Proteopedia - User contributions [en]

Molecular Playground/CsoR and RcnR

2013-12-17T18:12:33Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']
[[Image:Ni-and-Co-Site.jpg|500px|left|thumb|Fig. 1: Schematic of known Ni(II) and Co(II) binding residues in the metal sites of RcnR. Figure made with ChemDraw.]]
RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref><ref>PMID: 22471551</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.

The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-31T14:42:13Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']
[[Image:Ni-and-Co-Site.jpg|500px|left|thumb|Fig. 1: Schematic of known Ni(II) and Co(II) binding residues in the metal sites of RcnR.]]
RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref><ref>PMID: 22471551</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.

The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-31T14:41:39Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']
[[Image:Ni-and-Co-Site.jpg|500px|left|thumb|Fig. 1: Schematic of known Ni(II) and Co(II) binding residues.]]
RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref><ref>PMID: 22471551</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.

The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

CBI Molecules

2013-10-30T18:29:46Z

Carolyn Carr:

These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].
Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground] (see also [[Molecular Playground|Molecular Playground in Proteopedia]]). Follow the links below to read nontechnical descriptions, in Proteopedia, of these molecules.

UMass CBI Members, add your molecules to the list (which is alphabetical by CBI research mentor); follow the instructions below the list.

Fall 2013: CBI Molecules are due 12/4/13 and should be added at the TOP of the list from your lab. Label it as "in progress" until you are finished, and then as "New 2013" or "Revised 2013". For those editing an existing CBI Molecule, start from that entry so that it retains the full author list of all authors that contributed (or include credits to the original page and authors if it does not).

==Molecules==
'''** Designates CBI Molecules Featured on [http://http://www.umass.edu/cbi/ CBI website]'''

Bhatia Lab

: '''[[Molecular Playground/Alginate-Fall2011]]''', Joe White, David Griffin

: '''[[Molecular Playground/Alginate-Fall2010]]''', Joe White, David Griffin

: '''[[Molecular Playground/Poly(ethylene glycol)]]''', Erika M. Saffer

[http://chamberslab.com/wp/ Chambers Lab]

: '''[[Molecular Playground/Glutamate Receptor]]''', Amanda Hussey, Steve McCarron, Rosie Combs-Bachmann, Mariel Feliciano

[http://www.chem.umass.edu/~chenlab/index.HTML Chen Lab]

: New Fall 2012!! '''[[Molecular Playground/OmpG]]''', Christina Chisholm

[http://openwetware.org/wiki/Chien Chien Lab]

: **'''[[Molecular Playground/Hexameric ClpX]]''', Joanne Lau
:: Best CBI Molecule 2011

: '''[[Molecular Playground/DNA replication initiator DnaA]]''', Jing Liu

Forbes Lab

: '''[[Molecular Playground/CheR]]''', Miaomin Zhang

: '''[[Molecular Playground/RBP]]''', Jan Panteli

: '''[[Molecular Playground/TRAIL]]''', Charley Swofford

[http://www.biochem.umass.edu/garman/index.html Garman Lab]

: '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon

: '''[[Molecular Playground/Human PPCA]]''', Nilima Kolli

[http://people.chem.umass.edu/gieraschlab/ Gierasch Lab]

: '''[[CRABP I ( Cellular Retinoic Acid Binding Protein )|Molecular Playground/CRABP I]]''', Kristine Faye Pobre, Mylene Ferrolino,Mangai Periasamy
:: Best Overall CBI Molecule 2010

: '''[[Molecular Playground/CRABP I (Cellular Retinoic Acid Binding Protein)]]''', Gustavo Elberto Epalza Sanchez
(compare this to the previous version above to see what's new)

: **'''[[Molecular_Playground/DHFR]]''', Karan Hingorani
:: Best CBI Molecule 2012

[http://people.chem.umass.edu/jhardy/ Hardy Lab]

: New Fall 2012!! ''' [[Molecular Playground/[[Caspase-3 Regulatory Mechanisms]]''', Scott Eron, Bay Serrano, Yunlong Zhao

: ''' [[Molecular Playground/Caspase-6 and neurodegeneration]]''', Kevin Buadlart Dagbay

: '''[[Molecular Playground/Caspase-7 Dynamics]]'''

: '''[[Molecular Playground/Caspase-9 Regulation]]''', Kristen Huber

: '''[[Molecular Playground/Caspase-6 (new)]]''', Elih Velazquez

: '''[[Molecular Playground/Influenza A M2 transmembrane domain]]''', Samantha Nicholls

: '''[[Molecular Playground/Dengue Virus Protease]]''', Muslum Yildiz

Hebert Lab

: New Fall 2012!! '''[[Molecular_Playground/ERDj5]]''', Lydia Lamriben
: '''[[Molecular Playground/Saposin C]]''', Abla Tannous
: '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd

[http://people.biochem.umass.edu/aheuck/aph.html Heuck Lab]

: Updated Fall 2012!! '''[[Molecular_Playground/Pcr H]]''', Fabian Romano, Carolina Morell-Pérez

[http://people.chem.umass.edu/mholden/ Holden Lab]

: New Fall 2012!! '''[[Molecular Playground/Protective Antigen]]''', Jing Huang

[http://www.chem.umass.edu/people/kaltashovlab/ Kaltashov Lab]

: Updated Fall 2012!! ''' [[Molecular Playground/Transferrin]]''', Khaja Muneeruddin, Jake Pawlowski

: '''[[Molecular Playground/Velaglucerase]]''', Adriana Kita

Knapp lab

: Updated Fall 2012!! '''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Cristina Martin, Serap Pektas
:: Best CBI Molecule Proteopedia Page 2010

: '''[[Molecular Playground/FIH]]''', Cornelius Taabazuing, Breanne Holmes, John Hangasky

[http://people.chem.umass.edu/mmaroney/ Maroney Lab]

: '''[[Molecular Playground/Nickel Superoxide Dismutase]]''', Carolyn Carr
: Updated Fall 2013!! '''[[Molecular Playground/CsoR and RcnR]]''', Heidi Hu, Carolyn Carr
: '''[[Molecular Playground/HypA]]''', Heidi Hu

[http://www.chem.umass.edu/~cmartin/ Martin Lab]

: **'''[[Molecular Playground/T7 RNAP Conformations]]''', Luis E. Ramirez-Tapia
:: Best CBI Molecule 2011
: '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia

: '''[[Molecular Playground/Human mtRNA pol]]''', Ketan Mathavan

Peyton Lab
: '''[[Molecular Playground/C-Raf]]''', Thuy Nguyen
: '''[[Molecular Playground/FAK]]''', Dannielle Ryman

[http://roberts.openwetware.org/ Roberts Lab]

: '''[[Molecular Playground/Taxol]]''', Rohan Patil, Sarah Wilson

: '''[[Molecular Playground/Insulin]]''', Whitney Stoppel

[http://www.umass.edu/rotellogroup/ Rotello Lab]

: '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Daniel Moyano-Marino

: '''[[Molecular Playground/Pancreatic Lipase]]''', Rui Tang

: '''[[Molecular playground/Chymotrypsin]]''', Brad

: '''[[Molecular Playground/Targeting Peptide]]''', David Solfiell

[https://elements.chem.umass.edu/schnarrlab/ Schnarr Lab]

: New Fall 2012!! '''[[Molecular Playground/4'-PHOSPHOPANTETHEINYL TRANSFERASE (Sfp)]]''', Jon Amoroso, Gitanjeli Prasad, Lawrence Sheringham Borketey

: '''[[6-deoxyerythronolide_B_synthase_(DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin, Jon Amoroso, Lawrence Sheringham Borketey

: '''[[Molecular Playground/ACP apo]]''', Gitanjeli Prasad

[http://www.biochem.umass.edu/faculty/danny-j-schnell Schnell Lab]
: New Fall 2012!! '''[[Molecular Playground/Tic40]]''', Mine Canakci

Tew Lab

: '''[[Molecular Playground/HIV Tat]]''', Brittany deRonde

Thayumanavan Lab

: '''[[Molecular Playground/Lysozyme ]]''', Daniella Gonzalez

: '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura

: '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi

: '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy

: '''[[Molecular Playground/Biotin binding avidin]]''', Diego Amado

: '''[[User:Jiaming Zhuang|Molecular Playground/MMP12]]''', Jiaming Zhuang

: ''' [[User:Jing Guo|Molecular Playground/Gluconase]]''', Jing Guo

: '''[[Molecular Playground/Glutathione Reductase]]''', Reuben Chacko

Thayumanavan & Vachet Labs

: '''[[Molecular Playground/Trypsin]]''', Gladys Murage

[http://people.chem.umass.edu/thompson/index.html Thompson] & [http://www.chem.umass.edu/~rmweis/weislab/ Weis] Labs

: New Fall 2012!! '''[[Molecular Playground/CheA]]''', Elizabeth R. Haglin

: '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Lynmarie K. Thompson, Shiela M. Jones

: '''[[Molecular Playground/cytoplasmic domain of a serine chemotaxis receptor]]''', Meili Yang

: '''[[Molecular Playground/Cytoplasmic domain of chemoreceptor of Thermotoga maritima]]''', Xuni Li

[http://www.chem.umass.edu/~vachet/index.html Vachet Lab]

: '''[[Molecular playground/beta 2 microglobulin]]''', Nick Borotto
:: Best CBI Molecule Jmol scenes 2010

: '''[[Molecular Playground/Myoglobin]]''', Yuping Zhou

:'''[[Molecular Playground/ Copper-Zinc Superoxide Dismutase]]''', Shaynah Browne

: New Fall 2012!! '''[[Molecular Playground/Ubiquitin salt bridge discussion]]''', Zhe Zhang

Other Molecules of interest

: '''[[Molecular Playground/PcrA Helicase]]''', Luis E Ramirez-Tapia, [http://www.chem.umass.edu/~cmartin/ Martin Lab]

Other Laboratories

: '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III, [http://www.bio.umass.edu/mcb/faculty/Shao.html Shao Lab]

: '''[[Molecular Playground/BLG|Molecular Playground/β-lactoglobulin]]''', Daniel Seeman, Dubin Lab

: '''[[Molecular Playground/ADAM13]]''', Genevieve Abbruzzese, Alfandari Lab

==Instructions==

'''The goal is for students to work collaboratively to create one excellent CBI Molecule for each CBI research group, to be featured on the CBI website.'''

Fall 2013: Complete steps 1-2 by 10/18, and bring your computer to the CBI Molecule Workshop on Wed 10/23 in ISB 321.

A successful CBI Molecule will be an interesting, nontechnical description of a molecule related to your group's research. It should not be super long, but instead have multiple green scenes. Green scenes should clearly show an interesting feature and should be attractive. Use the green scenes to help you make interesting points about the molecule (do not try to describe every feature of the molecule). It's great if you can end with a brief statement about how it relates to your group's research goals.

1. If you don't already have one, request a Proteopedia account and log in.

2. Read through the rest of the instructions and look at any existing CBI Molecules from your research group. Talk with other Chalk Talk students in your research group and think about how you can make a new or improved CBI Molecule related to your group's research. Develop ideas for the scenes you wish to show. You will work learn how to make scenes during the workshop.

3. Get started working in Proteopedia by using the links at [[Help:Contents]]. Make yourself a sandbox page: Enter "User:Your Name/Sandbox 1" (omit quotes) in the search box, then follow instructions to edit this page. Practice entering text, inserting a structure window with scrolling text (green 4-square button on the right), and creating a green scene. You can look at other Proteopedia pages in edit mode to see how different effects (like colored text) are achieved (but this won't show you how the scene effects are made).

4. For those editing an existing CBI Molecule, start from that entry so that it retains the full author list of all authors that contributed. You are encouraged to collaborate on the CBI Molecules, but everyone will need to do some editing of the molecule so that they each appear as authors on the final list. If you are the sole student from your group enrolled in Chalk Talk and have not previously made a CBI Molecule, try to convince another group member who has previously made a CBI Molecule (see list above) to join us for the workshop so that you can work together.

5. Your final pages should be called "Molecular Playground/your molecule" and should have links on this CBI Molecule page -- put the new ones first on the list from your research group. Label them "in progress" until you are finished, and then "new 2013" or "revised 2013".

==Links to HELP pages==
Overview at [[Help:Contents ]]

See also [[Help:Getting_Started_in_Proteopedia]]

Videos showing how to use Proteopedia:
[[Proteopedia:Video_Guide]]
(Sometimes slow -- if you pause the video and wait awhile it will download and then you can play it without interruptions)

[[Proteopedia:DIY:Scenes|Proteopedia Scenes: Do It Yourself]]
gives succinct step by step instructions on how to create a molecular scene.

A powerpoint-like set of slides that walks a user through the process of creating a new page and a new molecular scene/green link.
[http://www.proteopedia.org/wiki/images/1/1b/2009_07_13_Proteopedia_Workshop.pdf Proteopedia Workshop Slides]

[[Proteopedia:Guidelines for Ethical Writing]].
Please pay attention to the section about images. There are links to examples of images re-used with explicit permission.

For other help resources, click on [[Help:Contents|Help]] in the ''navigation'' box at the upper left of every page in Proteopedia.

CBI Molecules

2013-10-30T17:35:12Z

Carolyn Carr:

These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].
Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground] (see also [[Molecular Playground|Molecular Playground in Proteopedia]]). Follow the links below to read nontechnical descriptions, in Proteopedia, of these molecules.

UMass CBI Members, add your molecules to the list (which is alphabetical by CBI research mentor); follow the instructions below the list.

Fall 2013: CBI Molecules are due 12/4/13 and should be added at the TOP of the list from your lab. Label it as "in progress" until you are finished, and then as "New 2013" or "Revised 2013". For those editing an existing CBI Molecule, start from that entry so that it retains the full author list of all authors that contributed (or include credits to the original page and authors if it does not).

==Molecules==
'''** Designates CBI Molecules Featured on [http://http://www.umass.edu/cbi/ CBI website]'''

Bhatia Lab

: '''[[Molecular Playground/Alginate-Fall2011]]''', Joe White, David Griffin

: '''[[Molecular Playground/Alginate-Fall2010]]''', Joe White, David Griffin

: '''[[Molecular Playground/Poly(ethylene glycol)]]''', Erika M. Saffer

[http://chamberslab.com/wp/ Chambers Lab]

: '''[[Molecular Playground/Glutamate Receptor]]''', Amanda Hussey, Steve McCarron, Rosie Combs-Bachmann, Mariel Feliciano

[http://www.chem.umass.edu/~chenlab/index.HTML Chen Lab]

: New Fall 2012!! '''[[Molecular Playground/OmpG]]''', Christina Chisholm

[http://openwetware.org/wiki/Chien Chien Lab]

: **'''[[Molecular Playground/Hexameric ClpX]]''', Joanne Lau
:: Best CBI Molecule 2011

: '''[[Molecular Playground/DNA replication initiator DnaA]]''', Jing Liu

Forbes Lab

: '''[[Molecular Playground/CheR]]''', Miaomin Zhang

: '''[[Molecular Playground/RBP]]''', Jan Panteli

: '''[[Molecular Playground/TRAIL]]''', Charley Swofford

[http://www.biochem.umass.edu/garman/index.html Garman Lab]

: '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon

: '''[[Molecular Playground/Human PPCA]]''', Nilima Kolli

[http://people.chem.umass.edu/gieraschlab/ Gierasch Lab]

: '''[[CRABP I ( Cellular Retinoic Acid Binding Protein )|Molecular Playground/CRABP I]]''', Kristine Faye Pobre, Mylene Ferrolino,Mangai Periasamy
:: Best Overall CBI Molecule 2010

: '''[[Molecular Playground/CRABP I (Cellular Retinoic Acid Binding Protein)]]''', Gustavo Elberto Epalza Sanchez
(compare this to the previous version above to see what's new)

: **'''[[Molecular_Playground/DHFR]]''', Karan Hingorani
:: Best CBI Molecule 2012

[http://people.chem.umass.edu/jhardy/ Hardy Lab]

: New Fall 2012!! ''' [[Molecular Playground/[[Caspase-3 Regulatory Mechanisms]]''', Scott Eron, Bay Serrano, Yunlong Zhao

: ''' [[Molecular Playground/Caspase-6 and neurodegeneration]]''', Kevin Buadlart Dagbay

: '''[[Molecular Playground/Caspase-7 Dynamics]]'''

: '''[[Molecular Playground/Caspase-9 Regulation]]''', Kristen Huber

: '''[[Molecular Playground/Caspase-6 (new)]]''', Elih Velazquez

: '''[[Molecular Playground/Influenza A M2 transmembrane domain]]''', Samantha Nicholls

: '''[[Molecular Playground/Dengue Virus Protease]]''', Muslum Yildiz

Hebert Lab

: New Fall 2012!! '''[[Molecular_Playground/ERDj5]]''', Lydia Lamriben
: '''[[Molecular Playground/Saposin C]]''', Abla Tannous
: '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd

[http://people.biochem.umass.edu/aheuck/aph.html Heuck Lab]

: Updated Fall 2012!! '''[[Molecular_Playground/Pcr H]]''', Fabian Romano, Carolina Morell-Pérez

[http://people.chem.umass.edu/mholden/ Holden Lab]

: New Fall 2012!! '''[[Molecular Playground/Protective Antigen]]''', Jing Huang

[http://www.chem.umass.edu/people/kaltashovlab/ Kaltashov Lab]

: Updated Fall 2012!! ''' [[Molecular Playground/Transferrin]]''', Khaja Muneeruddin, Jake Pawlowski

: '''[[Molecular Playground/Velaglucerase]]''', Adriana Kita

Knapp lab

: Updated Fall 2012!! '''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Cristina Martin, Serap Pektas
:: Best CBI Molecule Proteopedia Page 2010

: '''[[Molecular Playground/FIH]]''', Cornelius Taabazuing, Breanne Holmes, John Hangasky

[http://people.chem.umass.edu/mmaroney/ Maroney Lab]

: New Fall 2012!! '''[[Molecular Playground/Nickel Superoxide Dismutase]]''', Carolyn Carr
: Updated Fall 2013!!'''[[Molecular Playground/CsoR and RcnR]]''', Heidi Hu, Carolyn Carr
: New Fall 2012!! '''[[Molecular Playground/HypA]]''', Heidi Hu

[http://www.chem.umass.edu/~cmartin/ Martin Lab]

: **'''[[Molecular Playground/T7 RNAP Conformations]]''', Luis E. Ramirez-Tapia
:: Best CBI Molecule 2011
: '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia

: '''[[Molecular Playground/Human mtRNA pol]]''', Ketan Mathavan

Peyton Lab
: '''[[Molecular Playground/C-Raf]]''', Thuy Nguyen
: '''[[Molecular Playground/FAK]]''', Dannielle Ryman

[http://roberts.openwetware.org/ Roberts Lab]

: '''[[Molecular Playground/Taxol]]''', Rohan Patil, Sarah Wilson

: '''[[Molecular Playground/Insulin]]''', Whitney Stoppel

[http://www.umass.edu/rotellogroup/ Rotello Lab]

: '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Daniel Moyano-Marino

: '''[[Molecular Playground/Pancreatic Lipase]]''', Rui Tang

: '''[[Molecular playground/Chymotrypsin]]''', Brad

: '''[[Molecular Playground/Targeting Peptide]]''', David Solfiell

[https://elements.chem.umass.edu/schnarrlab/ Schnarr Lab]

: New Fall 2012!! '''[[Molecular Playground/4'-PHOSPHOPANTETHEINYL TRANSFERASE (Sfp)]]''', Jon Amoroso, Gitanjeli Prasad, Lawrence Sheringham Borketey

: '''[[6-deoxyerythronolide_B_synthase_(DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin, Jon Amoroso, Lawrence Sheringham Borketey

: '''[[Molecular Playground/ACP apo]]''', Gitanjeli Prasad

[http://www.biochem.umass.edu/faculty/danny-j-schnell Schnell Lab]
: New Fall 2012!! '''[[Molecular Playground/Tic40]]''', Mine Canakci

Tew Lab

: '''[[Molecular Playground/HIV Tat]]''', Brittany deRonde

Thayumanavan Lab

: '''[[Molecular Playground/Lysozyme ]]''', Daniella Gonzalez

: '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura

: '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi

: '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy

: '''[[Molecular Playground/Biotin binding avidin]]''', Diego Amado

: '''[[User:Jiaming Zhuang|Molecular Playground/MMP12]]''', Jiaming Zhuang

: ''' [[User:Jing Guo|Molecular Playground/Gluconase]]''', Jing Guo

: '''[[Molecular Playground/Glutathione Reductase]]''', Reuben Chacko

Thayumanavan & Vachet Labs

: '''[[Molecular Playground/Trypsin]]''', Gladys Murage

[http://people.chem.umass.edu/thompson/index.html Thompson] & [http://www.chem.umass.edu/~rmweis/weislab/ Weis] Labs

: New Fall 2012!! '''[[Molecular Playground/CheA]]''', Elizabeth R. Haglin

: '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Lynmarie K. Thompson, Shiela M. Jones

: '''[[Molecular Playground/cytoplasmic domain of a serine chemotaxis receptor]]''', Meili Yang

: '''[[Molecular Playground/Cytoplasmic domain of chemoreceptor of Thermotoga maritima]]''', Xuni Li

[http://www.chem.umass.edu/~vachet/index.html Vachet Lab]

: '''[[Molecular playground/beta 2 microglobulin]]''', Nick Borotto
:: Best CBI Molecule Jmol scenes 2010

: '''[[Molecular Playground/Myoglobin]]''', Yuping Zhou

:'''[[Molecular Playground/ Copper-Zinc Superoxide Dismutase]]''', Shaynah Browne

: New Fall 2012!! '''[[Molecular Playground/Ubiquitin salt bridge discussion]]''', Zhe Zhang

Other Molecules of interest

: '''[[Molecular Playground/PcrA Helicase]]''', Luis E Ramirez-Tapia, [http://www.chem.umass.edu/~cmartin/ Martin Lab]

Other Laboratories

: '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III, [http://www.bio.umass.edu/mcb/faculty/Shao.html Shao Lab]

: '''[[Molecular Playground/BLG|Molecular Playground/β-lactoglobulin]]''', Daniel Seeman, Dubin Lab

: '''[[Molecular Playground/ADAM13]]''', Genevieve Abbruzzese, Alfandari Lab

==Instructions==

'''The goal is for students to work collaboratively to create one excellent CBI Molecule for each CBI research group, to be featured on the CBI website.'''

Fall 2013: Complete steps 1-2 by 10/18, and bring your computer to the CBI Molecule Workshop on Wed 10/23 in ISB 321.

A successful CBI Molecule will be an interesting, nontechnical description of a molecule related to your group's research. It should not be super long, but instead have multiple green scenes. Green scenes should clearly show an interesting feature and should be attractive. Use the green scenes to help you make interesting points about the molecule (do not try to describe every feature of the molecule). It's great if you can end with a brief statement about how it relates to your group's research goals.

1. If you don't already have one, request a Proteopedia account and log in.

2. Read through the rest of the instructions and look at any existing CBI Molecules from your research group. Talk with other Chalk Talk students in your research group and think about how you can make a new or improved CBI Molecule related to your group's research. Develop ideas for the scenes you wish to show. You will work learn how to make scenes during the workshop.

3. Get started working in Proteopedia by using the links at [[Help:Contents]]. Make yourself a sandbox page: Enter "User:Your Name/Sandbox 1" (omit quotes) in the search box, then follow instructions to edit this page. Practice entering text, inserting a structure window with scrolling text (green 4-square button on the right), and creating a green scene. You can look at other Proteopedia pages in edit mode to see how different effects (like colored text) are achieved (but this won't show you how the scene effects are made).

4. For those editing an existing CBI Molecule, start from that entry so that it retains the full author list of all authors that contributed. You are encouraged to collaborate on the CBI Molecules, but everyone will need to do some editing of the molecule so that they each appear as authors on the final list. If you are the sole student from your group enrolled in Chalk Talk and have not previously made a CBI Molecule, try to convince another group member who has previously made a CBI Molecule (see list above) to join us for the workshop so that you can work together.

5. Your final pages should be called "Molecular Playground/your molecule" and should have links on this CBI Molecule page -- put the new ones first on the list from your research group. Label them "in progress" until you are finished, and then "new 2013" or "revised 2013".

==Links to HELP pages==
Overview at [[Help:Contents ]]

See also [[Help:Getting_Started_in_Proteopedia]]

Videos showing how to use Proteopedia:
[[Proteopedia:Video_Guide]]
(Sometimes slow -- if you pause the video and wait awhile it will download and then you can play it without interruptions)

[[Proteopedia:DIY:Scenes|Proteopedia Scenes: Do It Yourself]]
gives succinct step by step instructions on how to create a molecular scene.

A powerpoint-like set of slides that walks a user through the process of creating a new page and a new molecular scene/green link.
[http://www.proteopedia.org/wiki/images/1/1b/2009_07_13_Proteopedia_Workshop.pdf Proteopedia Workshop Slides]

[[Proteopedia:Guidelines for Ethical Writing]].
Please pay attention to the section about images. There are links to examples of images re-used with explicit permission.

For other help resources, click on [[Help:Contents|Help]] in the ''navigation'' box at the upper left of every page in Proteopedia.

CBI Molecules

2013-10-30T17:34:31Z

Carolyn Carr:

These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].
Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground] (see also [[Molecular Playground|Molecular Playground in Proteopedia]]). Follow the links below to read nontechnical descriptions, in Proteopedia, of these molecules.

UMass CBI Members, add your molecules to the list (which is alphabetical by CBI research mentor); follow the instructions below the list.

Fall 2013: CBI Molecules are due 12/4/13 and should be added at the TOP of the list from your lab. Label it as "in progress" until you are finished, and then as "New 2013" or "Revised 2013". For those editing an existing CBI Molecule, start from that entry so that it retains the full author list of all authors that contributed (or include credits to the original page and authors if it does not).

==Molecules==
'''** Designates CBI Molecules Featured on [http://http://www.umass.edu/cbi/ CBI website]'''

Bhatia Lab

: '''[[Molecular Playground/Alginate-Fall2011]]''', Joe White, David Griffin

: '''[[Molecular Playground/Alginate-Fall2010]]''', Joe White, David Griffin

: '''[[Molecular Playground/Poly(ethylene glycol)]]''', Erika M. Saffer

[http://chamberslab.com/wp/ Chambers Lab]

: '''[[Molecular Playground/Glutamate Receptor]]''', Amanda Hussey, Steve McCarron, Rosie Combs-Bachmann, Mariel Feliciano

[http://www.chem.umass.edu/~chenlab/index.HTML Chen Lab]

: New Fall 2012!! '''[[Molecular Playground/OmpG]]''', Christina Chisholm

[http://openwetware.org/wiki/Chien Chien Lab]

: **'''[[Molecular Playground/Hexameric ClpX]]''', Joanne Lau
:: Best CBI Molecule 2011

: '''[[Molecular Playground/DNA replication initiator DnaA]]''', Jing Liu

Forbes Lab

: '''[[Molecular Playground/CheR]]''', Miaomin Zhang

: '''[[Molecular Playground/RBP]]''', Jan Panteli

: '''[[Molecular Playground/TRAIL]]''', Charley Swofford

[http://www.biochem.umass.edu/garman/index.html Garman Lab]

: '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon

: '''[[Molecular Playground/Human PPCA]]''', Nilima Kolli

[http://people.chem.umass.edu/gieraschlab/ Gierasch Lab]

: '''[[CRABP I ( Cellular Retinoic Acid Binding Protein )|Molecular Playground/CRABP I]]''', Kristine Faye Pobre, Mylene Ferrolino,Mangai Periasamy
:: Best Overall CBI Molecule 2010

: '''[[Molecular Playground/CRABP I (Cellular Retinoic Acid Binding Protein)]]''', Gustavo Elberto Epalza Sanchez
(compare this to the previous version above to see what's new)

: **'''[[Molecular_Playground/DHFR]]''', Karan Hingorani
:: Best CBI Molecule 2012

[http://people.chem.umass.edu/jhardy/ Hardy Lab]

: New Fall 2012!! ''' [[Molecular Playground/[[Caspase-3 Regulatory Mechanisms]]''', Scott Eron, Bay Serrano, Yunlong Zhao

: ''' [[Molecular Playground/Caspase-6 and neurodegeneration]]''', Kevin Buadlart Dagbay

: '''[[Molecular Playground/Caspase-7 Dynamics]]'''

: '''[[Molecular Playground/Caspase-9 Regulation]]''', Kristen Huber

: '''[[Molecular Playground/Caspase-6 (new)]]''', Elih Velazquez

: '''[[Molecular Playground/Influenza A M2 transmembrane domain]]''', Samantha Nicholls

: '''[[Molecular Playground/Dengue Virus Protease]]''', Muslum Yildiz

Hebert Lab

: New Fall 2012!! '''[[Molecular_Playground/ERDj5]]''', Lydia Lamriben
: '''[[Molecular Playground/Saposin C]]''', Abla Tannous
: '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd

[http://people.biochem.umass.edu/aheuck/aph.html Heuck Lab]

: Updated Fall 2012!! '''[[Molecular_Playground/Pcr H]]''', Fabian Romano, Carolina Morell-Pérez

[http://people.chem.umass.edu/mholden/ Holden Lab]

: New Fall 2012!! '''[[Molecular Playground/Protective Antigen]]''', Jing Huang

[http://www.chem.umass.edu/people/kaltashovlab/ Kaltashov Lab]

: Updated Fall 2012!! ''' [[Molecular Playground/Transferrin]]''', Khaja Muneeruddin, Jake Pawlowski

: '''[[Molecular Playground/Velaglucerase]]''', Adriana Kita

Knapp lab

: Updated Fall 2012!! '''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Cristina Martin, Serap Pektas
:: Best CBI Molecule Proteopedia Page 2010

: '''[[Molecular Playground/FIH]]''', Cornelius Taabazuing, Breanne Holmes, John Hangasky

[http://people.chem.umass.edu/mmaroney/ Maroney Lab]

: New Fall 2012!! '''[[Molecular Playground/Nickel Superoxide Dismutase]]''', Carolyn Carr
: '''[[Molecular Playground/CsoR and RcnR]]''', Heidi Hu, Carolyn Carr
: New Fall 2012!! '''[[Molecular Playground/HypA]]''', Heidi Hu

[http://www.chem.umass.edu/~cmartin/ Martin Lab]

: **'''[[Molecular Playground/T7 RNAP Conformations]]''', Luis E. Ramirez-Tapia
:: Best CBI Molecule 2011
: '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia

: '''[[Molecular Playground/Human mtRNA pol]]''', Ketan Mathavan

Peyton Lab
: '''[[Molecular Playground/C-Raf]]''', Thuy Nguyen
: '''[[Molecular Playground/FAK]]''', Dannielle Ryman

[http://roberts.openwetware.org/ Roberts Lab]

: '''[[Molecular Playground/Taxol]]''', Rohan Patil, Sarah Wilson

: '''[[Molecular Playground/Insulin]]''', Whitney Stoppel

[http://www.umass.edu/rotellogroup/ Rotello Lab]

: '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Daniel Moyano-Marino

: '''[[Molecular Playground/Pancreatic Lipase]]''', Rui Tang

: '''[[Molecular playground/Chymotrypsin]]''', Brad

: '''[[Molecular Playground/Targeting Peptide]]''', David Solfiell

[https://elements.chem.umass.edu/schnarrlab/ Schnarr Lab]

: New Fall 2012!! '''[[Molecular Playground/4'-PHOSPHOPANTETHEINYL TRANSFERASE (Sfp)]]''', Jon Amoroso, Gitanjeli Prasad, Lawrence Sheringham Borketey

: '''[[6-deoxyerythronolide_B_synthase_(DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin, Jon Amoroso, Lawrence Sheringham Borketey

: '''[[Molecular Playground/ACP apo]]''', Gitanjeli Prasad

[http://www.biochem.umass.edu/faculty/danny-j-schnell Schnell Lab]
: New Fall 2012!! '''[[Molecular Playground/Tic40]]''', Mine Canakci

Tew Lab

: '''[[Molecular Playground/HIV Tat]]''', Brittany deRonde

Thayumanavan Lab

: '''[[Molecular Playground/Lysozyme ]]''', Daniella Gonzalez

: '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura

: '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi

: '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy

: '''[[Molecular Playground/Biotin binding avidin]]''', Diego Amado

: '''[[User:Jiaming Zhuang|Molecular Playground/MMP12]]''', Jiaming Zhuang

: ''' [[User:Jing Guo|Molecular Playground/Gluconase]]''', Jing Guo

: '''[[Molecular Playground/Glutathione Reductase]]''', Reuben Chacko

Thayumanavan & Vachet Labs

: '''[[Molecular Playground/Trypsin]]''', Gladys Murage

[http://people.chem.umass.edu/thompson/index.html Thompson] & [http://www.chem.umass.edu/~rmweis/weislab/ Weis] Labs

: New Fall 2012!! '''[[Molecular Playground/CheA]]''', Elizabeth R. Haglin

: '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Lynmarie K. Thompson, Shiela M. Jones

: '''[[Molecular Playground/cytoplasmic domain of a serine chemotaxis receptor]]''', Meili Yang

: '''[[Molecular Playground/Cytoplasmic domain of chemoreceptor of Thermotoga maritima]]''', Xuni Li

[http://www.chem.umass.edu/~vachet/index.html Vachet Lab]

: '''[[Molecular playground/beta 2 microglobulin]]''', Nick Borotto
:: Best CBI Molecule Jmol scenes 2010

: '''[[Molecular Playground/Myoglobin]]''', Yuping Zhou

:'''[[Molecular Playground/ Copper-Zinc Superoxide Dismutase]]''', Shaynah Browne

: New Fall 2012!! '''[[Molecular Playground/Ubiquitin salt bridge discussion]]''', Zhe Zhang

Other Molecules of interest

: '''[[Molecular Playground/PcrA Helicase]]''', Luis E Ramirez-Tapia, [http://www.chem.umass.edu/~cmartin/ Martin Lab]

Other Laboratories

: '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III, [http://www.bio.umass.edu/mcb/faculty/Shao.html Shao Lab]

: '''[[Molecular Playground/BLG|Molecular Playground/β-lactoglobulin]]''', Daniel Seeman, Dubin Lab

: '''[[Molecular Playground/ADAM13]]''', Genevieve Abbruzzese, Alfandari Lab

==Instructions==

'''The goal is for students to work collaboratively to create one excellent CBI Molecule for each CBI research group, to be featured on the CBI website.'''

Fall 2013: Complete steps 1-2 by 10/18, and bring your computer to the CBI Molecule Workshop on Wed 10/23 in ISB 321.

A successful CBI Molecule will be an interesting, nontechnical description of a molecule related to your group's research. It should not be super long, but instead have multiple green scenes. Green scenes should clearly show an interesting feature and should be attractive. Use the green scenes to help you make interesting points about the molecule (do not try to describe every feature of the molecule). It's great if you can end with a brief statement about how it relates to your group's research goals.

1. If you don't already have one, request a Proteopedia account and log in.

2. Read through the rest of the instructions and look at any existing CBI Molecules from your research group. Talk with other Chalk Talk students in your research group and think about how you can make a new or improved CBI Molecule related to your group's research. Develop ideas for the scenes you wish to show. You will work learn how to make scenes during the workshop.

3. Get started working in Proteopedia by using the links at [[Help:Contents]]. Make yourself a sandbox page: Enter "User:Your Name/Sandbox 1" (omit quotes) in the search box, then follow instructions to edit this page. Practice entering text, inserting a structure window with scrolling text (green 4-square button on the right), and creating a green scene. You can look at other Proteopedia pages in edit mode to see how different effects (like colored text) are achieved (but this won't show you how the scene effects are made).

4. For those editing an existing CBI Molecule, start from that entry so that it retains the full author list of all authors that contributed. You are encouraged to collaborate on the CBI Molecules, but everyone will need to do some editing of the molecule so that they each appear as authors on the final list. If you are the sole student from your group enrolled in Chalk Talk and have not previously made a CBI Molecule, try to convince another group member who has previously made a CBI Molecule (see list above) to join us for the workshop so that you can work together.

5. Your final pages should be called "Molecular Playground/your molecule" and should have links on this CBI Molecule page -- put the new ones first on the list from your research group. Label them "in progress" until you are finished, and then "new 2013" or "revised 2013".

==Links to HELP pages==
Overview at [[Help:Contents ]]

See also [[Help:Getting_Started_in_Proteopedia]]

Videos showing how to use Proteopedia:
[[Proteopedia:Video_Guide]]
(Sometimes slow -- if you pause the video and wait awhile it will download and then you can play it without interruptions)

[[Proteopedia:DIY:Scenes|Proteopedia Scenes: Do It Yourself]]
gives succinct step by step instructions on how to create a molecular scene.

A powerpoint-like set of slides that walks a user through the process of creating a new page and a new molecular scene/green link.
[http://www.proteopedia.org/wiki/images/1/1b/2009_07_13_Proteopedia_Workshop.pdf Proteopedia Workshop Slides]

[[Proteopedia:Guidelines for Ethical Writing]].
Please pay attention to the section about images. There are links to examples of images re-used with explicit permission.

For other help resources, click on [[Help:Contents|Help]] in the ''navigation'' box at the upper left of every page in Proteopedia.

Molecular Playground/CsoR and RcnR

2013-10-30T17:33:58Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref><ref>PMID: 22471551</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.
[[Image:Ni-and-Co-Site.jpg|500px|left|thumb|Fig. 1: Schematic of known Ni(II) and Co(II) binding residues.]]
The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T17:33:28Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref><ref>PMID: 22471551</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.
[[Image:Ni-and-Co-Site.jpg|500px|left|thumb|Fig. 1: Schematic of known Ni(II) binding residues.]]
The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T17:33:13Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref><ref>PMID: 22471551</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.
[[Image:Ni-and-Co-Site.jpg|300px|left|thumb|Fig. 1: Schematic of known Ni(II) binding residues.]]
The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T17:32:56Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref><ref>PMID: 22471551</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.
[[Image:Ni-and-Co-Site.jpg|150px|left|thumb|Fig. 1: Schematic of known Ni(II) binding residues.]]
The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T17:32:16Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref><ref>PMID: 22471551</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.
[[Image:Ni-and-Co-Site.png|150px|left|thumb|Fig. 1: Schematic of known Ni(II) binding residues.]]
The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T17:31:42Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref><ref>PMID: 22471551</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.
[[Image:Ni and Co Site.png|150px|left|thumb|Fig. 1: Schematic of known Ni(II) binding residues.]]
The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T17:17:20Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref><ref>PMID: 22471551</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.
[[Image:Ni Site.png|150px|left|thumb|Fig. 1: Schematic of known Ni(II) binding residues.]]
The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T17:12:35Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref><ref>PMID: 22471551</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.
[[Image:Ni Site.png|200px|thumb|Fig. 1: Schematic of known Ni(II) binding residues.]]
The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T17:12:10Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref><ref>PMID: 22471551</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.

The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

[[Image:Ni Site.png|300px|thumb|Fig. 1: Schematic of known Ni(II) binding residues.]]

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T16:07:16Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref><ref>PMID: 22471551</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.

The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T16:06:07Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>PMID: 23215580</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.

The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T16:04:47Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64.<ref>dx.doi.org/10.1021/bi300886q</ref> Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.

The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T16:03:25Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64. Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.

The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

<ref>dx.doi.org/10.1021/bi300886q</ref>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T15:57:05Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64. Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there are a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.

The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding. Identification of the remaining metal binding residues in RcnR is ongoing, in addition to identification of the DNA-binding residues in RcnR, as there is no crystal structure of any member of this family of proteins binding to DNA.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T15:53:28Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64. Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there is a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.

The Co(II) site is bound by the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T15:51:24Z

Carolyn Carr:

----
<applet load='2hh7' size='[400,388]' frame='true' align='right'
caption='Cu(I)-bound CsoR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2HH7 2HH7])' />

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

== Introduction ==

Heavy metals such as iron, nickel, copper, and zinc are important cofactors for the functions of many different metalloenzymes. High levels of these heavy metals can also cause damage to cellular components, therefore intracellular levels of metals are tightly regulated within the cell. One of the ways that bacteria can regulate intracellular metal levels is by increasing the amount of metal efflux proteins. CsoR and RcnR are members of a large family of metal-responsive DNA-binding proteins, both of which regulate the transcription of metal-specific efflux proteins. CsoR is only responsive to the binding of Cu(I); whereas RcnR is only responsive to the binding of Ni(II) or Co(II).<ref>PMID:21511390</ref>

== RcnR and CsoR ==

In [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] apo-RcnR blocks the transcription of nickel and cobalt efflux proteins RcnA and RcnB by binding to its promoter region. Although no crystal structure of RcnR is available on the PDB, the Cu(I)-bound CsoR crystal structure from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is available and RcnR is predicted to share a similar fold to CsoR. Upon Ni(II)- or Co(II)-binding, RcnR is released from DNA allowing the transcription of RcnA and RcnB, facilitating the efflux of Ni(II) and Co(II).<ref>PMID:20442957</ref> CsoR has been characterized in [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis'']<ref>PMID:18048925</ref> and [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']<ref>PMID:17143269</ref> to release from the promoter regions of copper-efflux operons upon binding of Cu(I). The analogous functions of CsoR and RcnR in addition to local sequence similarity (25% identical, 56% similar) suggests a conserved mode of function in this family of metal-responsive DNA-binding proteins.<ref>PMID:18505253</ref>

== Structure of CsoR and RcnR ==

<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/1'>Tetrameric CsoR</scene> binds one Cu(I) per monomer. The protein forms a dimer of dimers with a
<scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/5'>pore</scene> in the tetrameric interface. Each <scene name='Heidi_Hu/Sandbox_1/Tetrameric_csor/10'>Cu(I) coordinated by two different monomers</scene> of a dimer unit. Where one monomer is bound to Cu(I) by His61 and Cys65, the other monomer is bound to the metal by Cys35.<ref>PMID:17143269</ref> [http://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']

RcnR is also tetrameric and has the same protein-to-metal stoichiometry. Through a combination of site-directed mutagenesis, lacZ activity assays and X-ray absorption spectroscopy (XAS) structural studies it is now known that RcnR uses a different ligand set to bind Ni(II) than it does Co(II).

The Ni(II) site is bound by the N-terminal amine, Cys35, and His64. Because the Ni(II) site has an octahedral geometry, there are three metal binding residues whose identity is unknown. However, using XAS and lacZ activity assays it is known that the remaining ligands bind to the Ni(II) using N/O atoms and that there is a total of two histidine ligand bound to the Ni(II), leaving the identity of one unaccounted for. Studies have shown that this histidine is not His3, His60, or His67.

The Co(II) site is bound the the N-terminal amine, His3, Cys35, His64 and possibly His60. The Co(II) site of RcnR also has an octahedral geometry, leaving 1-2 residues whose identity is unknown. XAS reveals that these ligands are bound to Co(II) using N/O atoms and that there are a total of three histidine ligands bound to the Co(II). Studies have shown that His67 is not a Co(II) ligand.

== Research Interests ==

The mechanism of DNA binding of the CsoR/RcnR family of metal-responsive transcriptional regulators is still unknown. Additionally, RcnR has an added level of complexity because it is reponsive to both Ni(II) and Co(II) binding. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in the conformational changes of RcnR induced by DNA-, Ni(II)-, and Co(II)-binding.

==3D structures of copper homeostasis protein==

[[Copper homeostasis protein]]

== References ==

<references/>

== Also See ==

[[2hh7]]

Molecular Playground/CsoR and RcnR

2013-10-30T15:25:02Z

Carolyn Carr:

Molecular Playground/Nickel Superoxide Dismutase

2013-10-23T16:44:27Z

Carolyn Carr:

----
Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

<Structure load='1q0m' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: [[1q0m]]). The yellow/red molecules represent sulphates, the grey/red molecules represent acetic acid, and the green spheres represent the nickel ions bound by the nickel-hook region.' scene='Insert optional scene name here' />

===Introduction===
----

'''Nickel Superoxide Dismutase''' (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the ping pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel is not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

===NiSOD Structure===
----

NiSOD is a homohexamer ('''Fig. 2''') composed of a <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_dimer/1'>dimer</scene> of <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_trimer/1'>trimers</scene> and binds <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_monomer/1'>one nickel ion per monomer</scene>. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-hook/1'>nickel-hook</scene>. The nickel in the active site cycles between Ni(II) and Ni(III). In <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-his_off2/1'>the Ni(II) state</scene> the nickel has a square planar geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-his_on/1'>oxidized to Ni(III)</scene>, the imidazole group of His1 binds in the axial position forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID [[1t6u]].]]

===Research Interests===
----

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===
----

<references/>

===See Also===
----

[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2013-01-04T01:35:34Z

Carolyn Carr:

----
Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

<Structure load='1q0m' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1Q0M). The yellow/red molecules represent sulphates, the grey/red molecules represent acetic acid, and the green spheres represent the nickel ions bound by the nickel-hook region.' scene='Insert optional scene name here' />

===Introduction===
----

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel is not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

===NiSOD Structure===
----

NiSOD is a homohexamer ('''Fig. 2''') composed of a <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_dimer/1'>dimer</scene> of <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_trimer/1'>trimers</scene> and binds <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_monomer/1'>one nickel ion per monomer</scene>. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-hook/1'>nickel-hook</scene>. The nickel in the active site cycles between Ni(II) and Ni(III). In <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-his_off2/1'>the Ni(II) state</scene> the nickel has a square planar geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-his_on/1'>oxidized to Ni(III)</scene>, the imidazole group of His1 binds in the axial position forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===
----

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===
----

<references/>

===See Also===
----

[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-12T20:24:10Z

Carolyn Carr:

----
Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

<Structure load='1q0m' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1Q0M). The yellow/red molecules represent sulphates, the grey/red molecules represent acetic acid, and the green spheres represent the nickel ions bound by the nickel-hook region.' scene='Insert optional scene name here' />

===Introduction===
----

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel is not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

===NiSOD Structure===
----

NiSOD is a homohexamer ('''Fig. 2''') composed of a <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_dimer/1'>dimer</scene> of <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_trimer/1'>trimers</scene> and binds <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_monomer/1'>one nickel ion per monomer</scene>. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-hook/1'>nickel-hook</scene>. The nickel in the active site cycles between Ni(II) and Ni(III). In <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-his_off2/1'>the Ni(II) state</scene> the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-his_on/1'>oxidized to Ni(III)</scene>, the imidazole group of His1 binds in the axial position forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===
----

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===
----

<references/>

===See Also===
----

[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

CBI Molecules

2012-12-12T01:17:03Z

Carolyn Carr:

These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].
Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground] (see also [[Molecular Playground|Molecular Playground in Proteopedia]]). Follow the links below to read nontechnical descriptions, in Proteopedia, of these molecules.

UMass CBI Members, add your molecules to the list (which is alphabetical by CBI research mentor); follow the instructions below the list.

Fall 2012: CBI Molecules are due 12/12/12 and should be added at the TOP of the list from your lab. Label it as "in progress" until you are finished. For those editing an existing CBI Molecule, start from that entry so that it retains the full author list of all authors that contributed (or include credits to the original page and authors if it does not -- I may be able to request additions to the author list).

==Molecules==
'''** Designates CBI Molecules Featured on [http://http://www.umass.edu/cbi/ CBI website]'''

Bhatia Lab

: '''[[Molecular Playground/Alginate-Fall2011]]''', Joe White, David Griffin

: '''[[Molecular Playground/Alginate-Fall2010]]''', Joe White, David Griffin

: '''[[Molecular Playground/Poly(ethylene glycol)]]''', Erika M. Saffer

[http://chamberslab.com/wp/ Chambers Lab]

: '''[[Molecular Playground/Glutamate Receptor]]''', Amanda Hussey, Steve McCarron, Rosie Combs-Bachmann, Mariel Feliciano

[http://openwetware.org/wiki/Chien Chien Lab]

: **'''[[Molecular Playground/Hexameric ClpX]]''', Joanne Lau
:: Best CBI Molecule 2011

: '''[[Molecular Playground/DNA replication initiator DnaA]]''', Jing Liu

Forbes Lab

: '''[[Molecular Playground/CheR]]''', Miaomin Zhang

: '''[[Molecular Playground/RBP]]''', Jan Panteli

: '''[[Molecular Playground/TRAIL]]''', Charley Swofford

[http://www.biochem.umass.edu/garman/index.html Garman Lab]

: '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon

: '''[[Molecular Playground/Human PPCA]]''', Nilima Kolli

[http://people.chem.umass.edu/gieraschlab/ Gierasch Lab]

: '''[[CRABP I ( Cellular Retinoic Acid Binding Protein )|Molecular Playground/CRABP I]]''', Kristine Faye Pobre, Mylene Ferrolino,Mangai Periasamy
:: Best Overall CBI Molecule 2010

: '''[[Molecular Playground/CRABP I (Cellular Retinoic Acid Binding Protein)]]''', Gustavo Elberto Epalza Sanchez
(compare this to the previous version above to see what's new)

: **'''[[Molecular_Playground/DHFR]]''', Karan Hingorani
:: Best CBI Molecule 2012

[http://people.chem.umass.edu/jhardy/ Hardy Lab]

: ''' [[Molecular Playground/Caspase-6 and neurodegeneration]]''', Kevin Buadlart Dagbay

: '''[[Molecular Playground/Caspase-7 Dynamics]]'''

: '''[[Molecular Playground/Caspase-9 Regulation]]''', Kristen Huber

: '''[[Molecular Playground/Caspase-6 (new)]]''', Elih Velazquez

: '''[[Molecular Playground/Influenza A M2 transmembrane domain]]''', Samantha Nicholls

: '''[[Molecular Playground/Dengue Virus Protease]]''', Muslum Yildiz

Hebert Lab

: '''[[Molecular Playground/Saposin C]]''', Abla Tannous
: '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd

[http://people.biochem.umass.edu/aheuck/aph.html Heuck Lab]

: '''[[Molecular_Playground/Pcr H]]''', Fabian Romano

[http://www.chem.umass.edu/people/kaltashovlab/ Kaltashov Lab]

: ''' [[Molecular Playground/Transferrin]]''', Khaja Muneeruddin

: '''[[Molecular Playground/Velaglucerase]]''', Adriana Kita

Knapp lab

:'''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Cristina Martin
:: Best CBI Molecule Proteopedia Page 2010

: '''[[Molecular Playground/FIH]]''', Cornelius Taabazuing, Breanne Holmes, John Hangasky

[http://people.chem.umass.edu/mmaroney/ Maroney Lab]

: '''[[Molecular Playground/Nickel Superoxide Dismutase]]''', Carolyn Carr
: '''[[Molecular Playground/CsoR and RcnR]]''', Heidi Hu

[http://www.chem.umass.edu/~cmartin/ Martin Lab]

: **'''[[Molecular Playground/T7 RNAP Conformations]]''', Luis E. Ramirez-Tapia
:: Best CBI Molecule 2011
: '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia

: '''[[Molecular Playground/Human mtRNA pol]]''', Ketan Mathavan

Peyton Lab
: '''[[Molecular Playground/C-Raf]]''', Thuy Nguyen
: '''[[Molecular Playground/FAK]]''', Dannielle Ryman

[http://roberts.openwetware.org/ Roberts Lab]

: '''[[Molecular Playground/Taxol]]''', Rohan Patil, Sarah Wilson

: '''[[Molecular Playground/Insulin]]''', Whitney Stoppel

[http://www.umass.edu/rotellogroup/ Rotello Lab]

: '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Daniel Moyano-Marino

: '''[[Molecular Playground/Pancreatic Lipase]]''', Rui Tang

: '''[[Molecular playground/Chymotrypsin]]''', Brad

: '''[[Molecular Playground/Targeting Peptide]]''', David Solfiell

Schnarr Lab

: '''[[6-deoxyerythronolide_B_synthase_(DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin, Jon Amoroso

: '''[[Molecular Playground/ACP apo]]''', Gitanjeli Prasad

Tew Lab

: '''[[Molecular Playground/HIV Tat]]''', Brittany deRonde

Thayumanavan Lab

: '''[[Molecular Playground/Lysozyme ]]''', Daniella Gonzalez

: '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura

: '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi

: '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy

: '''[[Molecular Playground/Biotin binding avidin]]''', Diego Amado

: '''[[User:Jiaming Zhuang|Molecular Playground/MMP12]]''', Jiaming Zhuang

: ''' [[User:Jing Guo|Molecular Playground/Gluconase]]''', Jing Guo

: '''[[Molecular Playground/Glutathione Reductase]]''', Reuben Chacko

Thayumanavan & Vachet Labs

: '''[[Molecular Playground/Trypsin]]''', Gladys Murage

[http://people.chem.umass.edu/thompson/index.html Thompson] & [http://www.chem.umass.edu/~rmweis/weislab/ Weis] Labs

: '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Lynmarie K. Thompson, Shiela M. Jones

: '''[[Molecular Playground/cytoplasmic domain of a serine chemotaxis receptor]]''', Meili Yang

: '''[[Molecular Playground/Cytoplasmic domain of chemoreceptor of Thermotoga maritima]]''', Xuni Li

[http://www.chem.umass.edu/~vachet/index.html Vachet Lab]

: '''[[Molecular playground/beta 2 microglobulin]]''', Nick Borotto
:: Best CBI Molecule Jmol scenes 2010

: '''[[Molecular Playground/Myoglobin]]''', Yuping Zhou

:'''[[Molecular Playground/ Copper-Zinc Superoxide Dismutase]]''', Shaynah Browne

Other Molecules of interest

: '''[[Molecular Playground/PcrA Helicase]]''', Luis E Ramirez-Tapia, [http://www.chem.umass.edu/~cmartin/ Martin Lab]

Other Laboratories

: '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III, [http://www.bio.umass.edu/mcb/faculty/Shao.html Shao Lab]

: '''[[Molecular Playground/BLG|Molecular Playground/β-lactoglobulin]]''', Daniel Seeman, Dubin Lab

: '''[[Molecular Playground/ADAM13]]''', Genevieve Abbruzzese, Alfandari Lab

==Instructions==

'''Congratulations to the prize-winning CBI molecules noted above! The new goal is for students to work collaboratively to create one excellent CBI Molecule for each CBI research group, to be featured on the CBI website.'''

Fall 2012: Complete steps 1-3 by 10/10/12, in preparation for the CBI Molecule Workshop.

1. If you don't already have one, request a Proteopedia account and log in.

2. Get started working in Proteopedia by using the links at [[Help:Contents]]. Make yourself a sandbox page: Enter "User:Your Name/Sandbox 1" (omit quotes) in the search box, then follow instructions to edit this page. Practice entering text, inserting a structure window with scrolling text (green 4-square button on the right), and creating a green scene. You can look at other Proteopedia pages in edit mode to see how different effects (like colored text) are achieved (but this won't show you how the scene effects are made).

3. Get together with the other Chalk Talk students in your research group and decide which molecule you will improve or create. Develop ideas for the scenes you wish to show. You will work on these during the workshop with our help, and then finish them on your own.

You are encouraged to collaborate on this year's CBI Molecules, but everyone will need to do some editing of the molecule so that they each appear as authors on the final list. If you are the sole student from your group enrolled in Chalk Talk and have not previously made a CBI Molecule, try to convince another group member who has previously made a CBI Molecule (see list above) to join us for the workshop so that you can work together.

A successful CBI Molecule will be an interesting, nontechnical description of a molecule related to your group's research. It should not be super long, but instead have multiple green scenes. Green scenes should clearly show an interesting feature and should be attractive. Use the green scenes to help you make interesting points about the molecule (do not try to describe every feature of the molecule). It's great if you can end with a brief statement about how it relates to your group's research goals.

4. Your final pages should be called "Molecular Playground/your molecule" and should have links on this CBI Molecule page -- put the new ones first on the list from your research group. Label them "in progress" until you are finished.

==Links to HELP pages==
Overview at [[Help:Contents ]]

See also [[Help:Getting_Started_in_Proteopedia]]

Videos showing how to use Proteopedia:
[[Proteopedia:Video_Guide]]
(Sometimes slow -- if you pause the video and wait awhile it will download and then you can play it without interruptions)

[[Proteopedia:DIY:Scenes|Proteopedia Scenes: Do It Yourself]]
gives succinct step by step instructions on how to create a molecular scene.

A powerpoint-like set of slides that walks a user through the process of creating a new page and a new molecular scene/green link.
[http://www.proteopedia.org/wiki/images/1/1b/2009_07_13_Proteopedia_Workshop.pdf Proteopedia Workshop Slides]

[[Proteopedia:Guidelines for Ethical Writing]].
Please pay attention to the section about images. There are links to examples of images re-used with explicit permission.

For other help resources, click on [[Help:Contents|Help]] in the ''navigation'' box at the upper left of every page in Proteopedia.

User:Carolyn Carr/Sandbox 1

2012-12-12T01:15:36Z

Carolyn Carr: User:Carolyn Carr/Sandbox 1 moved to Molecular Playground/Nickel Superoxide Dismutase

#REDIRECT [[Molecular Playground/Nickel Superoxide Dismutase]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-12T01:15:36Z

Carolyn Carr: User:Carolyn Carr/Sandbox 1 moved to Molecular Playground/Nickel Superoxide Dismutase

----
Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

<Structure load='1q0m' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1Q0M). The yellow/red molecules represent sulphates, the grey/red molecules represent acetic acid, and the green spheres represent the nickel ions bound by the nickel-hook region.' scene='Insert optional scene name here' />

===Introduction===
----

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

===NiSOD Structure===
----

NiSOD is a homohexamer ('''Fig. 2''') composed of a <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_dimer/1'>dimer</scene> of <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_trimer/1'>trimers</scene> and binds <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_monomer/1'>one nickel ion per monomer</scene>. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-hook/1'>nickel-hook</scene>. The nickel in the active site cycles between Ni(II) and Ni(III). In <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-his_off2/1'>the Ni(II) state</scene> the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-his_on/1'>oxidized to Ni(III)</scene>, the imidazole group of His1 binds in the axial position forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===
----

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===
----

<references/>

===See Also===
----

[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-12T01:11:44Z

Carolyn Carr:

----
Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

<Structure load='1q0m' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1Q0M). The yellow/red molecules represent sulphates, the grey/red molecules represent acetic acid, and the green spheres represent the nickel ions bound by the nickel-hook region.' scene='Insert optional scene name here' />

===Introduction===
----

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

===NiSOD Structure===
----

NiSOD is a homohexamer ('''Fig. 2''') composed of a <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_dimer/1'>dimer</scene> of <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_trimer/1'>trimers</scene> and binds <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_monomer/1'>one nickel ion per monomer</scene>. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-hook/1'>nickel-hook</scene>. The nickel in the active site cycles between Ni(II) and Ni(III). In <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-his_off2/1'>the Ni(II) state</scene> the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-his_on/1'>oxidized to Ni(III)</scene>, the imidazole group of His1 binds in the axial position forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===
----

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===
----

<references/>

===See Also===
----

[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-12T01:11:17Z

Carolyn Carr:

----
Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

<Structure load='1q0m' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1Q0M). The yellow/red molecules represent sulphates, the grey/red molecules represent acetic acid, and the green spheres represent the nickel ions bound by the nickel-hook region.' scene='Insert optional scene name here' />

===Introduction===
----

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===
----

NiSOD is a homohexamer ('''Fig. 2''') composed of a <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_dimer/1'>dimer</scene> of <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_trimer/1'>trimers</scene> and binds <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_monomer/1'>one nickel ion per monomer</scene>. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-hook/1'>nickel-hook</scene>. The nickel in the active site cycles between Ni(II) and Ni(III). In <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-his_off2/1'>the Ni(II) state</scene> the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When <scene name='User:Carolyn_Carr/Sandbox_1/Nickel-his_on/1'>oxidized to Ni(III)</scene>, the imidazole group of His1 binds in the axial position forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===
----

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===
----

<references/>

===See Also===
----

[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-12T00:44:15Z

Carolyn Carr:

----
Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

<Structure load='1q0m' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1Q0M). The yellow/red molecules represent sulphates, the grey/red molecules represent acetic acid, and the green spheres represent the nickel ions bound by the nickel-hook region.' scene='Insert optional scene name here' />

===Introduction===
----

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===
----

NiSOD is a <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_hexamer/1'>homohexamer</scene> ('''Fig. 2''') composed of a <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_dimer/1'>dimer</scene> of <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_trimer/1'>trimers</scene> and binds <scene name='User:Carolyn_Carr/Sandbox_1/Nisod_monomer/1'>one nickel ion per monomer</scene>. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===
----

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===
----

<references/>

===See Also===
----

[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T23:21:29Z

Carolyn Carr:

----
Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

<Structure load='1q0m' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1Q0M). The yellow/red molecules represent sulphates, the grey/red molecules represent acetic acid, and the green spheres represent the nickel ions bound by the nickel-hook region.' scene='Insert optional scene name here' />

===Introduction===
----

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===
----

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===
----

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===
----

<references/>

===See Also===
----

[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T23:19:11Z

Carolyn Carr:

----
Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

<Structure load='1q0m' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1Q0M)' scene='Insert optional scene name here' />

===Introduction===
----

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===
----

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===
----

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===
----

<references/>

===See Also===
----

[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T23:18:49Z

Carolyn Carr:

----
Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

<Structure load='1t6u' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1Q0M)' scene='Insert optional scene name here' />

===Introduction===
----

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===
----

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===
----

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===
----

<references/>

===See Also===
----

[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T23:14:23Z

Carolyn Carr:

----
Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

<Structure load='1t6u' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1T6U)' scene='Insert optional scene name here' />

===Introduction===
----

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===
----

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===
----

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===
----

<references/>

===See Also===
----

[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T23:13:48Z

Carolyn Carr:

----
Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

<Structure load='1t6u' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1T6U)' scene='Insert optional scene name here' />

===Introduction===
----

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===
----

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===

<references/>

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T23:12:57Z

Carolyn Carr:

----
Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

==Molecular Playground/Nickel Superoxide Dismutase==

<Structure load='1t6u' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1T6U)' scene='Insert optional scene name here' />

===Introduction===

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===

<references/>

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T23:10:46Z

Carolyn Carr:

==Molecular Playground/Nickel Superoxide Dismutase==

<Structure load='1t6u' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1T6U)' scene='Insert optional scene name here' />

Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

===Introduction===

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===

<references/>

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T23:10:09Z

Carolyn Carr:

==Molecular Playground/Nickel Superoxide Dismutase==

<Structure load='1t6u' size='350' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1T6U)' scene='Insert optional scene name here' />

Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

===Introduction===

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]] 

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===

<references/>

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T23:09:31Z

Carolyn Carr:

==Molecular Playground/Nickel Superoxide Dismutase==

<Structure load='1t6u' size='400' frame='true' align='left' caption='Ni-bound NiSOD (PDB ID: 1T6U)' scene='Insert optional scene name here' />

Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

===Introduction===

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]]

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===

<references/>

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T23:07:50Z

Carolyn Carr:

==Molecular Playground/Nickel Superoxide Dismutase==

<Structure load='1t6u' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />

Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

===Introduction===

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]]

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===

<references/>

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T23:07:05Z

Carolyn Carr:

==Molecular Playground/Nickel Superoxide Dismutase==

Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

<Structure load='1t6u' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />

===Introduction===

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]]

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===

<references/>

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T23:01:00Z

Carolyn Carr:

==Molecular Playground/Nickel Superoxide Dismutase==

Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

===Introduction===

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]]

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref> Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===

<references/>

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T23:00:07Z

Carolyn Carr:

==Molecular Playground/Nickel Superoxide Dismutase==

Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

===Introduction===

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]]

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').[<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref>] Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref> In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===

<references/>

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T22:59:25Z

Carolyn Carr:

==Molecular Playground/Nickel Superoxide Dismutase==

Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

===Introduction===

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]]

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').[<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref>] Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines.<ref>PMID: 9878406</ref>, <ref>PMID: 1394426</ref>, <ref>PMID: 7849024</ref>] In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===

<references/>

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T22:53:32Z

Carolyn Carr:

==Molecular Playground/Nickel Superoxide Dismutase==

Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

===Introduction===

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]]

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').[<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref>] Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines. In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===

<references/>

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T22:53:00Z

Carolyn Carr:

==Molecular Playground/Nickel Superoxide Dismutase==

Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

===Introduction===

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]]

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').[<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref>] Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV].<ref>Uedsemma, M., Tamm, T. (Density-functional theory calculations of aqueous redox potentials of fourth-period transition metals. J. Phys. Chem. A. 2003 Aug 4;107:9997-10003. Epub 2003 Oct 23. 10.1021/jp0362741</ref> The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines. In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===

<references/>

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T22:36:57Z

Carolyn Carr:

==Molecular Playground/Nickel Superoxide Dismutase==

Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

===Introduction===

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]]

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').[<ref>PMID: 1094908</ref>-<ref>PMID: 11912934</ref>] Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV]. The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines. In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===

<references/>

1. Fridovich, I. (1975) Superoxide dismutases. ''Ann. Rev. Biochem.'', '''44''', 147-149. PMID: 1094908 

2. Lee, J.-W., Rue, J.-H., Kang, S. O. (2002) Nickel-containing superoxide dismutase. ''Methods Enzymol.'', '''349''', 90-101.

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]

Molecular Playground/Nickel Superoxide Dismutase

2012-12-11T22:35:32Z

Carolyn Carr:

==Molecular Playground/Nickel Superoxide Dismutase==

Nickel superoxide dismutase (NiSOD) is one of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts, Amherst Chemistry-Biology Interface Program] at Umass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

===Introduction===

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O2 and H2O2 with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

[[Image:SODs.png|600 px|thumb|'''Fig. 1:''' Active site structures of the four known SOD's.]]

:M(n + 1) + O2•- → Mn+ + O2 
Mn+ + O2•- + 2H+ → M(n + 1) + H2O2 
————————————————— 
:2O2•- + 2H+ → O2 + H2O2 

NiSOD is unique among SOD's for a variety of reasons. 
NiSOD shares no sequence homology with the [http://en.wikipedia.org/wiki/Superoxide_dismutase other known SOD's] ('''Fig. 1''').[<ref>PMID: 1094908</ref>-<ref>2</ref>] Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV]. The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines. In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand ('''Fig. 1'''). 

===NiSOD Structure===

NiSOD is a homohexamer ('''Fig. 2''') composed of a dimer of trimers and binds one nickel ion per monomer. The residues coordinated to the nickel active site are located within the first six N-terminal amino acids, termed the nickel-hook. The nickel in the active site cycles between Ni(II) and Ni(III). In the Ni(II) state the nickel has a square pyramidal geometry and is coordinated by the side chains of Cys2 and Cys5 as well as the N-terminal amine and the backbone amide group of Cys2. When oxidized to Ni(III) the imidazole group of His1 binds in the axial position, forming a square pyramidal geometry.

[[Image:NiSOD Hexamer.png|300 px|thumb|Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.]]

===Research Interests===

The [http://people.chem.umass.edu/mmaroney/research.html | Maroney Lab] is currently investigating the details of the NiSOD catalytic mechanism, including how the enzyme maintains its nickel active sites at 50% Ni(II)/Ni(III) equilibrium despite strong oxidation. In addition, efforts are currently underway to characterize a previously observed intermediate.

===References===
1. Fridovich, I. (1975) Superoxide dismutases. ''Ann. Rev. Biochem.'', '''44''', 147-149. PMID: 1094908 

2. Lee, J.-W., Rue, J.-H., Kang, S. O. (2002) Nickel-containing superoxide dismutase. ''Methods Enzymol.'', '''349''', 90-101.

===See Also===
[[1t6i]] 
[[1t6q]] 
[[1t6u]] 
[[3g4x]] 
[[3g4z]] 
[[3g50]]