Proteopedia - User contributions [en]

CBI Molecules

2014-12-10T21:49:47Z

Jill Graham:

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 2014: CBI Molecules are due 12/3/14 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 2014" or "Revised 2014". For those editing an existing CBI Molecule, start by making a copy of that entry (leaving the original intact) so that it retains the full author list of all authors that contributed (or include credits and a link to the original page and authors if it does not).
Follow the instructions at the bottom of this page.

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

[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]

: '''[[Molecular Playground/ClyA]]''', Bib Yang
: '''[[Molecular Playground/OmpG]]''', Christina Chisholm

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

: '''[[Molecular Playground/ClpP]]''', Lisa Hernandez, Rob Vass '''New 2014'''
: '''[[Molecular Playground/Homo-dimeric RcdA]]''', Kamal K. Joshi
: **'''[[Molecular Playground/Hexameric ClpX]]''', Joanne Lau '''Best CBI Molecule 2011'''
: '''[[Molecular Playground/DNA replication initiator DnaA]]''', Jing Liu

Farkas Lab
: '''[[Molecular Playground/CLOCK:BMAL1 heterodimer complex]]''', Hui-Hsien Lin, Joseph Hardie, Michael Mingroni '''New 2014'''

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]

: '''[[Molecular_Playground/DnaK]]''', Joseph Tilitsky, New 2014
: '''[[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
: **'''[[Molecular_Playground/DHFR]]''', Karan Hingorani '''Best CBI Molecule 2012'''

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

: '''[[Molecular Playground/Executioner Caspase-7]]''', Derek MacPherson, Maureen E. Hill
: '''[[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

: '''[[Molecular_Playground/Hsp70-Hsp90]]''', Jill Graham "Revised 2014"
: '''[[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]

: '''[[Molecular_Playground/Pcr H]]''', Fabian Romano, Carolina Morell-Pérez, Yuzhou Tang

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

: '''[[Molecular Playground/Protective Antigen]]''', Jing Huang

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

: '''[http://proteopedia.org/wiki/index.php/Chengfeng_Ren Molecular Playground/Inteferon]'''[Revised], Chengfeng Ren
: ''' [[Molecular Playground/Transferrin]]''', Khaja Muneeruddin, Jake Pawlowski
: '''[[Molecular Playground/Velaglucerase]]''', Adriana Kita
: '''[[Molecular Playground/Antithrombin-Heparin]]''', Yunlong Zhao

[http://people.chem.umass.edu/knapplab/?q=knappchem/index.html/ Knapp Lab]
: '''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Cristina Martin, Serap Pektas '''Best CBI Molecule Proteopedia Page 2010''' '''***New Fall 2014***'''
: '''[[Molecular Playground/FIH]]''', Vanessa Chaplin, Cornelius Taabazuing, Breanne Holmes, John Hangasky

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

: '''[[Molecular Playground/UreE]]''', Priyanka Basak, '''New 2014'''
: '''[[Molecular Playground/Nickel Superoxide Dismutase]]''', Carolyn Carr
: '''[[Molecular Playground/CsoR and RcnR]]''', Heidi Hu, Carolyn Carr, Hsin-Ting (Tiffany )Huang, '''Revised 2014'''
: '''[[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

[http://www.peytonlab.org/ Peyton Lab]
: '''[[Molecular Playground/IntegrinBeta1]]''', Lauren Jansen, Lauren Barney, Elizabeth Brooks, Alyssa Schwartz ***'''NEW FALL 2014''''***
: '''[[Molecular Playground/MMP14]]''', Lauren Jansen
: '''[[Molecular Playground/C-Raf]]''', Thuy Nguyen
: '''[[Molecular Playground/FAK]]''', Dannielle Ryman

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

: '''[[Molecular Playground/Taxol]]''', Elizabeth Cummings, Rohan Patil, Sarah Wilson ***'''Revised Fall 2014'''***
: '''[[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

[http://http://www.umass.edu/schiffman/ Schiffman Lab]
: '''[[Molecular Playground/Streptavidin]]''', Katrina Rieger

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

Tew Lab

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

Thayumanavan Lab
: '''[[Interleukin-1 beta]]''', Huan He
: '''[[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 Lab]

: '''[[Molecular Playground/Bacterial Chemotaxis Complex]]''', Elizabeth R. Haglin, Maryam Kashefi
: '''[[Molecular Playground/CheA]]''', Elizabeth R. Haglin
: '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Lynmarie K. Thompson, Shiela M. Jones
: '''[[Molecular Playground/Cytoplasmic domain of chemoreceptor of Thermotoga maritima]]''', Xuni Li

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

: '''[[Molecular Playground/Human Serum Albumin]]''', Mahalia Serrano ''*Revised 2014*''
: '''[[Molecular playground/beta 2 microglobulin]]''', Nick Borotto, Tyler Marcinko ***'''Revised Fall 2014'''*** '''Best CBI Molecule Jmol scenes 2010'''
: '''[[Molecular Playground/Myoglobin]]''', Yuping Zhou
:'''[[Molecular Playground/ Copper-Zinc Superoxide Dismutase]]''', Shaynah Browne
: '''[[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/4'-PHOSPHOPANTETHEINYL TRANSFERASE (Sfp)]]''', Jon Amoroso, Gitanjeli Prasad, Lawrence Sheringham Borketey, Schnarr lab
: '''[[6-deoxyerythronolide_B_synthase_(DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin, Jon Amoroso, Lawrence Sheringham Borketey, Schnarr lab
: '''[[Molecular Playground/ACP apo]]''', Gitanjeli Prasad, Schnarr lab

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

: '''[[Molecular Playground/Alginate-Fall2011]]''', Joe White, David Griffi, Bhatia Lab
: '''[[Molecular Playground/Poly(ethylene glycol)]]''', Erika M. Saffer, Bhatia Lab

: '''[[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 2014: Complete steps 1-3 before the CBI Molecule Workshop on 11/19; bring your computer to the CBI Molecule Workshop in ISB 321. You will be able to start work on your CBI Molecule at the workshop. You should plan to stay and finish your molecule after the workshop (or as soon as possible) while the instructions and ideas are fresh in your mind.

A successful CBI Molecule is an interesting, nontechnical description of a molecule related to your group's research. It should tell an interesting story with few words and many green scenes. Green scenes should be clear and attractive illustrations that tell your story. 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, do the tutorials below, and look at any existing CBI Molecules from your research group. Talk with other CBI students in your research group and decide how you will collaborate to make an improved CBI Molecule related to your group's research. Develop ideas for the scenes that each of you will make.

3. Get started working in Proteopedia. 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. Explore the HELP links below to learn how to make 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).

'''Complete the above steps before the CBI Molecule Workshop.'''

4. When editing an existing CBI Molecule, leave the original intact and make a copy that you will edit 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 log in as themself and create a green scene to get credit for their work and to 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 2014" or "revised 2014". Minimize text; tell your story with green scenes!

6. When your CBI Molecule is complete, send Lynmarie an email to nominate a cool scene/clever caption you would like to feature at the Molecular Playground (include a link to your CBI Molecule, name of the green scene, and caption).

==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/Hsp70-Hsp90

2014-12-03T21:52:08Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
HoP is an adaptor protein that mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on HoP, but how HoP mediates this dual chaperone binding was unclear until structural studies of HoP were conducted. HoP is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR motifs are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. HoP is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains: TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
<scene name='56/566505/Tpr1/4'>TPR1</scene> consists of 3 <scene name='56/566505/Tpr_motifs/3'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70 (motifs are colored red, blue, and purple respectively, and the C-terminal capping helix is shown in green). Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 heptapeptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved <scene name='56/566505/Cbxy_clamp/10'>two-carboxylate clamp</scene> anchors the EEVD peptide motif of Hsp70 to TPR1 (residues highlighted in orange).

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2014-12-03T21:48:50Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
HoP is an adaptor protein that mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on HoP, but how HoP mediates this dual chaperone binding was unclear until structural studies of HoP were conducted. HoP is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR motifs are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. HoP is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains: TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
<scene name='56/566505/Tpr1/4'>TPR1</scene> consists of 3 <scene name='56/566505/Tpr_motifs/3'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70 (motifs are colored red, blue, and purple respectively, and the C-terminal capping helix is shown in green). Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 heptapeptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved <scene name='56/566505/Cbxy_clamp/6'>two-carboxylate clamp</scene> anchors the EEVD peptide motif of Hsp70 to TPR1 (residues highlighted in orange).

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2014-12-03T21:46:10Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
HoP is an adaptor protein that mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on HoP, but how HoP mediates this dual chaperone binding was unclear until structural studies of HoP were conducted. HoP is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR motifs are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. HoP is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains: TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
<scene name='56/566505/Tpr1/4'>TPR1</scene> consists of 3 <scene name='56/566505/Tpr_motifs/3'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70 (motifs are colored red, blue, and purple respectively, and the C-terminal capping helix is shown in green). Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 heptapeptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved <scene name='56/566505/Cbxy_clamp/5'>two-carboxylate clamp</scene> anchors the EEVD peptide motif of Hsp70 to TPR1 (residues highlighted in orange).

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2014-12-03T21:30:55Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
HoP is an adaptor protein that mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on HoP, but how HoP mediates this dual chaperone binding was unclear until structural studies of HoP were conducted. HoP is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR motifs are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. HoP is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains: TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
<scene name='56/566505/Tpr1/4'>TPR1</scene> consists of 3 <scene name='56/566505/Tpr_motifs/3'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70 (motifs are colored red, blue, and purple respectively, and the C-terminal capping helix is shown in green). Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 heptapeptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved <scene name='56/566505/Cbxy_clamp/4'>two-carboxylate clamp</scene> anchors the EEVD peptide motif of Hsp70 to TPR1 (residues highlighted in orange).

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2014-12-03T20:38:38Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
HoP is an adaptor protein that mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on HoP, but how HoP mediates this dual chaperone binding was unclear until structural studies of HoP were conducted. HoP is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR motifs are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. HoP is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains: TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
<scene name='56/566505/Tpr1/4'>TPR1</scene> consists of 3 <scene name='56/566505/Tpr_motifs/3'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70 (motifs are colored red, blue, and purple respectively, and the C-terminal capping helix is shown in green). Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 heptapeptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved <scene name='56/566505/Cbxy_clamp/3'>two-carboxylate clamp</scene> anchors the EEVD peptide motif of Hsp70 to TPR1 (residues highlighted in orange).

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2014-12-03T20:33:25Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
HoP is an adaptor protein that mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on HoP, but how HoP mediates this dual chaperone binding was unclear until structural studies of HoP were conducted. HoP is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR motifs are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. HoP is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains: TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
<scene name='56/566505/Tpr1/4'>TPR1</scene> consists of 3 <scene name='56/566505/Tpr_motifs/2'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70 (motifs are colored red, blue, and purple respectively, and the C-terminal capping helix is shown in green). Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 heptapeptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved <scene name='56/566505/Cbxy_clamp/3'>two-carboxylate clamp</scene> anchors the EEVD peptide motif of Hsp70 to TPR1 (residues highlighted in orange).

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2014-12-03T20:24:05Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein that mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this dual chaperone binding was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains: TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
<scene name='56/566505/Tpr1/2'>TPR1</scene> consists of 3 <scene name='56/566505/Tpr_motifs/2'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70 (motifs are colored red, blue, and purple respectively, and the C-terminal capping helix is shown in green). Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 heptapeptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved <scene name='56/566505/Cbxy_clamp/3'>two-carboxylate clamp</scene> anchors the EEVD peptide motif of Hsp70 to TPR1 (residues highlighted in orange).

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2014-12-03T20:20:50Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/3' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein that mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this dual chaperone binding was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains: TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
<scene name='56/566505/Tpr1/2'>TPR1</scene> consists of 3 <scene name='56/566505/Tpr_motifs/2'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70 (motifs are colored red, blue, and purple respectively, and the C-terminal capping helix is shown in green). Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 heptapeptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved <scene name='56/566505/Cbxy_clamp/3'>two-carboxylate clamp</scene> anchors the EEVD peptide motif of Hsp70 to TPR1 (residues highlighted in orange).

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T16:44:34Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/2' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein that mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this dual chaperone binding was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains: TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
<scene name='56/566505/Tpr1/2'>TPR1</scene> consists of 3 <scene name='56/566505/Tpr_motifs/2'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70 (motifs are colored red, blue, and purple respectively, and the C-terminal capping helix is shown in green). Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 heptapeptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved <scene name='56/566505/Cbxy_clamp/3'>two-carboxylate clamp</scene> anchors the EEVD peptide motif of Hsp70 to TPR1 (residues highlighted in orange).

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T16:39:25Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/2' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein that mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this dual chaperone binding was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains: TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
<scene name='56/566505/Tpr1/2'>TPR1</scene> consists of 3 <scene name='56/566505/Tpr_motifs/2'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70 (motifs are colored red, blue, and purple respectively, and the C-terminal capping helix is shown in green). Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 heptapeptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved <scene name='56/566505/Cbxy_clamp/2'>two-carboxylate clamp</scene> anchors the EEVD peptide motif of Hsp70 to TPR1 (residues highlighted in pink).

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T16:36:02Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/2' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein that mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains: TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
<scene name='56/566505/Tpr1/2'>TPR1</scene> consists of 3 <scene name='56/566505/Tpr_motifs/2'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved <scene name='56/566505/Cbxy_clamp/2'>two-carboxylate clamp</scene> anchors the EEVD peptide motif of Hsp70 to TPR1 (residues highlighted in pink).

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T16:34:05Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/2' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein that mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains: TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 <scene name='56/566505/Tpr_motifs/2'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved <scene name='56/566505/Cbxy_clamp/2'>two-carboxylate clamp</scene> anchors the EEVD peptide motif of Hsp70 to TPR1 (residues highlighted in pink).

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T16:29:52Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/2' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 <scene name='56/566505/Tpr_motifs/2'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T16:28:27Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/2' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 <scene name='56/566505/Tpr_motifs/1'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T16:22:12Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/1' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 <scene name='56/566505/Tpr_motifs/1'>TPR motifs</scene> and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T16:21:06Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Tpr1/1' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T03:23:11Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='TPR1' scene='56/566505/Hop_tpr1/1' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T03:22:02Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]' scene='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T03:18:53Z

Jill Graham:

<Structure load='56/566505/Hop_tpr1/1' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T03:17:16Z

Jill Graham:

<Structure load='56/566505/Hop_tpr1/1' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /><Structure load='1elr' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]'

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T03:16:08Z

Jill Graham:

<Structure load='1elr' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /><Structure load='1elr' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]' scene='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T03:09:57Z

Jill Graham:

<Structure load='56/566505/Hop_tpr1/1' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /><Structure load

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
<scene name='56/566505/Hop_tpr1/1'>TPR1</scene> consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T03:01:17Z

Jill Graham:

<Structure load='56/566505/Hop_tpr1/1' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /><Structure load

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T03:00:20Z

Jill Graham:

<Structure load='56/566505/Hop_tpr1/1' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /><Structure load='<scene name='56/566505/Hop_tpr1/1'>TextToBeDisplayed</scene>' size='500' frame='true' align='right'

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T02:58:43Z

Jill Graham:

<Structure load='<scene name='56/566505/Hop_tpr1/1'>TextToBeDisplayed</scene>' size='500' frame='true' align='right'

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T02:57:27Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]' <scene name='56/566505/Hop_tpr1/1'>TPR1</scene>

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T02:56:16Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]' <scene name='56/566505/Hop_tpr1/1'>TextToBeDisplayed</scene>

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T02:53:21Z

Jill Graham:

<Structure load='<scene name='56/566505/Hop_tpr1/1'>TextToBeDisplayed</scene> size='500' frame='true' align='right' caption='Insert caption here' scene='<='56/566505/Hop_tpr1/1'>TextToBeDisplayed</scene>' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T02:52:17Z

Jill Graham:

<Structure load=' size='500' frame='true' align='right' caption='Insert caption here' scene='<='56/566505/Hop_tpr1/1'>TextToBeDisplayed</scene>' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T02:51:00Z

Jill Graham:

<Structure load=' size='500' frame='true' align='right' caption='Insert caption here' scene='<scene name='56/566505/Hop_tpr1/1'>TextToBeDisplayed</scene>' /><Structure load='1elr' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]' scene='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. D'Andrea, L. Regan, L. TiBS Review; 28:12. 2003

2. Scheufler, C. et. al. Cell; 101:199-210. 2000

3. Zeytuni, N. et. al. Cell Structure; 20. 2012

Molecular Playground/Hsp70-Hsp90

2013-12-04T02:34:43Z

Jill Graham:

Molecular Playground/Hsp70-Hsp90

2013-12-04T02:06:50Z

Jill Graham:

<Structure load='1elr' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /><Structure load='1elr' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]' scene='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutation studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (GSGSGPTIEEVD). Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle. Additionally, a highly conserved two-carboxylate clamp anchors the EEVD peptide motif of Hsp70 to TPR1.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==References==

1. Hagiwara M. et. al. Molecular Cell; 41. 2011

2. Ushioda R. et. al. Science; 321. 2008

Molecular Playground/Hsp70-Hsp90

2013-12-04T00:49:02Z

Jill Graham:

<Structure load='1elr' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /><Structure load='1elr' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]' scene='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutations studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (. Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==Function==
ERdj5 is believed to play a critical role in ERAD (ER Associated Degradation) in that it is required for reducing ERAD substrates and facilitating their retrotranslocation from the ER to the cytoplasm. It has been shown to interact with EDEM (ER Degradation Enhancing Mannosidase), a protein that recognizes misfolded substrates and targets them for ERAD.

==References==

1. Hagiwara M. et. al. Molecular Cell; 41. 2011

2. Ushioda R. et. al. Science; 321. 2008

Molecular Playground/Hsp70-Hsp90

2013-12-04T00:46:11Z

Jill Graham:

<Structure load='1elr' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]' scene='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction with the C terminus of Hsp70. Mutations studies showed that the binding of TPR1 to Hsp70 is dependent upon the interaction between the TPR1 domain and a 12-mer C-terminal peptide of Hsp70 (. Shown to the right is the crystallized TPR1 with its respective Hsp70 peptide partner. TPR1 forms a cradle-like structure that accommodates the Hsp70 peptide in an extended conformation, and the peptide makes contact with only the sidechains of the helices in TPR1 that face the inner surface of the cradle.

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==Function==
ERdj5 is believed to play a critical role in ERAD (ER Associated Degradation) in that it is required for reducing ERAD substrates and facilitating their retrotranslocation from the ER to the cytoplasm. It has been shown to interact with EDEM (ER Degradation Enhancing Mannosidase), a protein that recognizes misfolded substrates and targets them for ERAD.

==References==

1. Hagiwara M. et. al. Molecular Cell; 41. 2011

2. Ushioda R. et. al. Science; 321. 2008

Molecular Playground/Hsp70-Hsp90

2013-12-03T21:33:57Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]' scene='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.

==TPR Domain 1 Structure==
TPR1 consists of 3 TPR motifs and is responsible for the interaction

<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==Function==
ERdj5 is believed to play a critical role in ERAD (ER Associated Degradation) in that it is required for reducing ERAD substrates and facilitating their retrotranslocation from the ER to the cytoplasm. It has been shown to interact with EDEM (ER Degradation Enhancing Mannosidase), a protein that recognizes misfolded substrates and targets them for ERAD.

==References==

1. Hagiwara M. et. al. Molecular Cell; 41. 2011

2. Ushioda R. et. al. Science; 321. 2008

Molecular Playground/Hsp70-Hsp90

2013-12-03T21:19:36Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]' scene='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/4' />

==Hsp70-Hsp90 Organizing Protein (Hop)==
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes.
==TPR Domain 1 Structure==
<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==Function==
ERdj5 is believed to play a critical role in ERAD (ER Associated Degradation) in that it is required for reducing ERAD substrates and facilitating their retrotranslocation from the ER to the cytoplasm. It has been shown to interact with EDEM (ER Degradation Enhancing Mannosidase), a protein that recognizes misfolded substrates and targets them for ERAD.

==References==

1. Hagiwara M. et. al. Molecular Cell; 41. 2011

2. Ushioda R. et. al. Science; 321. 2008

Molecular Playground/Hsp70-Hsp90

2013-12-03T20:51:47Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]' scene='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/4' />

==Hsp-70-Hsp-90 Organizing Protein==

==TPR Domain 1 Structure==
<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==Function==
ERdj5 is believed to play a critical role in ERAD (ER Associated Degradation) in that it is required for reducing ERAD substrates and facilitating their retrotranslocation from the ER to the cytoplasm. It has been shown to interact with EDEM (ER Degradation Enhancing Mannosidase), a protein that recognizes misfolded substrates and targets them for ERAD.

==References==

1. Hagiwara M. et. al. Molecular Cell; 41. 2011

2. Ushioda R. et. al. Science; 321. 2008

Molecular Playground/Hsp70-Hsp90

2013-12-03T20:50:56Z

Jill Graham: /* ERdj5 Structure */

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]' scene='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/4' />

==Hsp-70-Hsp-90 Organizing Protein==
<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==Function==
ERdj5 is believed to play a critical role in ERAD (ER Associated Degradation) in that it is required for reducing ERAD substrates and facilitating their retrotranslocation from the ER to the cytoplasm. It has been shown to interact with EDEM (ER Degradation Enhancing Mannosidase), a protein that recognizes misfolded substrates and targets them for ERAD.

==References==

1. Hagiwara M. et. al. Molecular Cell; 41. 2011

2. Ushioda R. et. al. Science; 321. 2008

Molecular Playground/Hsp70-Hsp90

2013-12-03T20:50:00Z

Jill Graham:

<Structure load='Insert PDB code or filename here' size='500' frame='true' align='right' caption='ERdj5 [[3apo]]' scene='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/4' />

==ERdj5 Structure==
<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs.

==Function==
ERdj5 is believed to play a critical role in ERAD (ER Associated Degradation) in that it is required for reducing ERAD substrates and facilitating their retrotranslocation from the ER to the cytoplasm. It has been shown to interact with EDEM (ER Degradation Enhancing Mannosidase), a protein that recognizes misfolded substrates and targets them for ERAD.

==References==

1. Hagiwara M. et. al. Molecular Cell; 41. 2011

2. Ushioda R. et. al. Science; 321. 2008

Molecular Playground/Hsp70-Hsp90

2013-12-03T20:31:09Z

Jill Graham:

<applet load='1elr' size='400' color='white' frame='true' align='right' caption='Dihydrofolate Reductase (DHFR)''/>

===TPR1 Domain of the Hsp-70-Hsp-90 Organizing Protein (HOP)===

<scene name='User:Karan_Hingorani/sandbox_2/Banner_1/1'>E. coli Dihydrofolate Reductase bound to Dihydrofolate and NADP+</scene>

Dihydrofolate Reductase (DHFR) is a crucial metabolic enzyme whose function is to reduce Dihydrofolate to Tetrahydrofolate, which can then be incorporated into the synthesis of Purines and amino acids. DHFR is classified as an oxidoreductase, which uses NADP+ as the electron acceptor (EC: 1.5.1.3). It is ubiquitously found and is now a popular target for anticancer drugs and antibiotics. <scene name='User:Karan_Hingorani/sandbox_2/Apo_dhfr/5'>Apo-DHFR</scene> free of any of its ligands is displayed here.[http://www.ncbi.nlm.nih.gov/pubmed/2185835?dopt=Abstract]

===Structure===

E.coli DHFR is a small 159 amino acid protein approximately 18kDa. It has an a/b structure with eight central B strands and four helices. The protein can be thought to be made up of two subdomains, divided by the active site cleft. The <scene name='User:Karan_Hingorani/sandbox_2/Ade_loop_1/1'>Adenosine binding loop</scene> which consists of residues 38-88 and the major subdomain comprised of about 100 residues. Three loops can be found in the major subdomain and they make up about 50% of this domain. They are the <scene name='User:Karan_Hingorani/sandbox_2/Met20_loop_1/1'>Met20 loop</scene> (residues 9-24), the <scene name='User:Karan_Hingorani/sandbox_2/Fg_loop_1/1'>F-G loop</scene> (residues 116-132)and the <scene name='User:Karan_Hingorani/sandbox_2/Gh_loop_1/1'>G-H loop</scene> (residues 142-150). The Met20 loop assumes different conformations during catalysis and accomodation of ligands is made possible by the 'hinge bending' motion about Lys 38 and Val 88 of the Adenosine binding domain.[http://www.ncbi.nlm.nih.gov/pubmed/15139807]

===Catalysis===

DHFR catalyzes the reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate using reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH). This system has been key model to decipher enzyme catalysis and the intermediates of the catalytic cycle have been identified by crystallography. CPMG relaxation NMR experiments have also revealed that intermediates in the catalytic cycle exist in equilibrium with the preceding or following intermediate. Thus the binding of ligands seems to happen via a conformational selection rather than the traditional view of induced fit which is used to explain conformation change on ligand binding.[http://www.sciencemag.org/content/313/5793/1638.short]. <scene name='User:Karan_Hingorani/sandbox_2/Lig_bound_1/1'>Holo DHFR</scene> shows the ligands Dihydrofolate and NADP+ positioned in the active site cleft.[http://www.ncbi.nlm.nih.gov/pubmed/2185835?dopt=Abstract]

===Drug Target===

Since DHFR is so critically positioned in the metabolic homeostasis of all organsims it has been the target of choice for anti microbial and anti cancer therapy. Inhibitors of this enzyme are essentially folate mimics, methotrexate which was first designed to inhibit <scene name='User:Karan_Hingorani/sandbox_2/Humandhfr_nad_metho_1/1'>Human DHFR</scene> and used as therapy for cancer and autoimmune disorders. Another folate mimic Trimethoprim was developed as an anti bacterial agent, having much more binding specificity to bacterial DHFR than its mammalian counterpart. Both drugs bind in the active site of the enzyme and are irreversibly bound thus ablating enzyme activity.[http://www.ncbi.nlm.nih.gov/pubmed/3054871] [http://www.ncbi.nlm.nih.gov/pubmed/15681865?dopt=Abstract].

===PDB structures===

[[5dfr]] - Apo E.coli DHFR

[[7dfr]] - E.coli DHFR bound to Folate and NADP+

[[1u72]] - Human DHFR bound to NADP+ and Methotrexate

There are several other structures for DHFR from Human, E.coli and other species but are not shown here. You may refer to the pdb website for those. [http://www.pdb.org/pdb/results/results.do?qrid=FE767C1F&tabtoshow=Current]

===See Also===

The wikipedia link on DHFR is also pretty useful for a general background.[[http://en.wikipedia.org/wiki/Dihydrofolate_reductase]]

===References===

1. Bystroff C. et al. Biochemistry 1990

2. Schnell JR. et al. Annu Rev Biophys Biomol Struct. 2004

3. Boehr DD. et al. Science 2006

4. Bystroff C. et al. Biochemistry 1990

5. Dauber-Osguthorpe P et al. Proteins 1988

6. Cody V. et al. Acta Crystallogr D Biol Crystallogr. 2005

Molecular Playground/Hsp70-Hsp90

2013-12-03T20:27:44Z

Jill Graham:

<applet load='1elr' size='400' color='white' frame='true' align='right' caption='Dihydrofolate Reductase (DHFR)''/>

Molecular Playground banner: DHFR, a central player in the synthesis of nucleic acids and amino acids

<scene name='User:Karan_Hingorani/sandbox_2/Banner_1/1'>E. coli Dihydrofolate Reductase bound to Dihydrofolate and NADP+</scene>

Dihydrofolate Reductase (DHFR) is a crucial metabolic enzyme whose function is to reduce Dihydrofolate to Tetrahydrofolate, which can then be incorporated into the synthesis of Purines and amino acids. DHFR is classified as an oxidoreductase, which uses NADP+ as the electron acceptor (EC: 1.5.1.3). It is ubiquitously found and is now a popular target for anticancer drugs and antibiotics. <scene name='User:Karan_Hingorani/sandbox_2/Apo_dhfr/5'>Apo-DHFR</scene> free of any of its ligands is displayed here.[http://www.ncbi.nlm.nih.gov/pubmed/2185835?dopt=Abstract]

===Structure===

E.coli DHFR is a small 159 amino acid protein approximately 18kDa. It has an a/b structure with eight central B strands and four helices. The protein can be thought to be made up of two subdomains, divided by the active site cleft. The <scene name='User:Karan_Hingorani/sandbox_2/Ade_loop_1/1'>Adenosine binding loop</scene> which consists of residues 38-88 and the major subdomain comprised of about 100 residues. Three loops can be found in the major subdomain and they make up about 50% of this domain. They are the <scene name='User:Karan_Hingorani/sandbox_2/Met20_loop_1/1'>Met20 loop</scene> (residues 9-24), the <scene name='User:Karan_Hingorani/sandbox_2/Fg_loop_1/1'>F-G loop</scene> (residues 116-132)and the <scene name='User:Karan_Hingorani/sandbox_2/Gh_loop_1/1'>G-H loop</scene> (residues 142-150). The Met20 loop assumes different conformations during catalysis and accomodation of ligands is made possible by the 'hinge bending' motion about Lys 38 and Val 88 of the Adenosine binding domain.[http://www.ncbi.nlm.nih.gov/pubmed/15139807]

===Catalysis===

DHFR catalyzes the reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate using reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH). This system has been key model to decipher enzyme catalysis and the intermediates of the catalytic cycle have been identified by crystallography. CPMG relaxation NMR experiments have also revealed that intermediates in the catalytic cycle exist in equilibrium with the preceding or following intermediate. Thus the binding of ligands seems to happen via a conformational selection rather than the traditional view of induced fit which is used to explain conformation change on ligand binding.[http://www.sciencemag.org/content/313/5793/1638.short]. <scene name='User:Karan_Hingorani/sandbox_2/Lig_bound_1/1'>Holo DHFR</scene> shows the ligands Dihydrofolate and NADP+ positioned in the active site cleft.[http://www.ncbi.nlm.nih.gov/pubmed/2185835?dopt=Abstract]

===Drug Target===

Since DHFR is so critically positioned in the metabolic homeostasis of all organsims it has been the target of choice for anti microbial and anti cancer therapy. Inhibitors of this enzyme are essentially folate mimics, methotrexate which was first designed to inhibit <scene name='User:Karan_Hingorani/sandbox_2/Humandhfr_nad_metho_1/1'>Human DHFR</scene> and used as therapy for cancer and autoimmune disorders. Another folate mimic Trimethoprim was developed as an anti bacterial agent, having much more binding specificity to bacterial DHFR than its mammalian counterpart. Both drugs bind in the active site of the enzyme and are irreversibly bound thus ablating enzyme activity.[http://www.ncbi.nlm.nih.gov/pubmed/3054871] [http://www.ncbi.nlm.nih.gov/pubmed/15681865?dopt=Abstract].

===PDB structures===

[[5dfr]] - Apo E.coli DHFR

[[7dfr]] - E.coli DHFR bound to Folate and NADP+

[[1u72]] - Human DHFR bound to NADP+ and Methotrexate

There are several other structures for DHFR from Human, E.coli and other species but are not shown here. You may refer to the pdb website for those. [http://www.pdb.org/pdb/results/results.do?qrid=FE767C1F&tabtoshow=Current]

===See Also===

The wikipedia link on DHFR is also pretty useful for a general background.[[http://en.wikipedia.org/wiki/Dihydrofolate_reductase]]

===References===

1. Bystroff C. et al. Biochemistry 1990

2. Schnell JR. et al. Annu Rev Biophys Biomol Struct. 2004

3. Boehr DD. et al. Science 2006

4. Bystroff C. et al. Biochemistry 1990

5. Dauber-Osguthorpe P et al. Proteins 1988

6. Cody V. et al. Acta Crystallogr D Biol Crystallogr. 2005

Molecular Playground/Hsp70-Hsp90

2013-12-03T18:37:28Z

Jill Graham:

* Full Real Name: Jill Graham

* Position: Graduate Student

* Institution (NO ABBREVIATIONS): University of Massachusetts, Amherst

* City, State/Province, Country: Amherst, Massachusetts USA

* Field of Expertise or Study: Biochemistry and Molecular Biology, Secretory Pathway and Adaptor Proteins