Proteopedia - User contributions [en]

Molecular Playground/Caspase-9 Regulation

2010-05-04T19:17:56Z

Kristen Huber: New page: One of the CBI Molecules being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at th...

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

Caspase-9 belongs to a family of "molecular scissors" called cysteine aspartate proteases. These proteases are the facilitators of apoptosis, the highly process of programmed cell death which is an important cellular process critical for normal development and stability of an organism.

Caspase-9 is regulated by controlling its multimeric state through monomer-dimer transitions. Caspase-9 exists as an inactive monomer and becomes active upon dimerization. It is in this dimeric state that caspase-9 can “cut” its intended protein partners (called substrates) at a specific amino acid sequence. X-linked inhibitors of apoptosis proteins, specifically the BIR3 domain, bind to monomeric caspase-9 to block dimerization thus preventing activation.

==Structure==

<applet load='1jxq' size='400' color='white' frame='true' align='right' caption='Caspase-9 Dimer'

scene='User:Kristen_Huber/Sandbox_1/Caspase-9_dimer/1'>Caspase-9 Molecular Playground</applet>

<scene name='User:Kristen_Huber/Sandbox_1/Caspase-9_dimer/1'>Caspase-9 Molecular Playground</scene>

Caspase-9 in the active, “prepared to cut” state, exists as a dimer. The dimer can be described as two monomers of a large and small subunit related by two-fold symmetry. The dimer is formed through interactions of the amino acids on a β-strand from each monomer which forms a continuous central β –sheet [1]. In addition, a seven residue loop also makes interactions across the interface. A loop bundle exists in this molecule as well and when properly ordered, it is able to “bind and cut” its substrate.

==Caspase-9/XIAP-BIR3 Interaction==

<applet load='1nw9' size='400' color='white' frame='true' align='right' caption='Caspase-9/XIAP-BIR3 Inhibitory Complex'

scene='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/1'>Caspase-9/XIAP BIR3 Molecular Playground</applet>

<scene name='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/1'>Caspase-9/XIAP BIR3 Molecular Playground</scene>

The protein-protein interface of the Caspase-9/XIAP BIR3 complex is dominated by a high level of shape complimentarily, a large collection of van der Walls contacts, and 11 intermolecular hydrogen bonds scattered throughout the entire 2200 Å2 interface of the complex [2]. This interaction prevents caspase-9 from dimerizing as well as prevents the organization of the loop bundle thus making the molecule inactive.

==See Also==

* http://www.pdb.org/pdb/explore/explore.do?structureId=1JXQ Cleaved Caspase-9 Dimer ( PDB ID ; 1JXQ) at RCSB PDB]
* http://www.pdb.org/pdb/explore/explore.do?structureId=1NW9 Caspase-9/XIAP BIR3 Inhibitory Complex ( PDB ID ; 1NW9) at RCSB PDB]

==References==
*[1] Renatus, M.; Stennicke, H. R.; Scott, F. L.; Liddington, R. C.; Salvesen, G. S., Dimer formation drives the activation of the cell death protease caspase 9. PNAS 2001, 98, (25), 14250.
*[2] Shiozaki, E. N.; Chai, J.; Rigotti, D. J.; Riedl, S. J.; Li, P.; Srinivasula, S. M.; Alnemri, E. S.; Fairman, R.; Shi, Y., Mechanism of XIAP-mediated inhibition of caspase-9. Molecular Cell 2003, 11, (2), 519-527.

CBI Molecules

2010-05-04T19:17:29Z

Kristen Huber:

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]. Follow the links below to read nontechnical descriptions in Proteopedia.

UMass CBI Members, add your molecules to the list; follow the instructions below the list.

'''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', [http://people.chem.umass.edu/thompson/index.html Thompson] & [http://www.chem.umass.edu/~rmweis/weislab/ Weis] laboratories

'''[[6-deoxyerythronolide B synthase (DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Schnarr lab (Tsung-Yi Lin)

'''[[Molecular Playground/Lysozime ]]''', Daniella Gonzalez, Thayumanavan Research Group

'''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura, Thayumanavan Research group

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

'''[[Molecular Playground/Taxol]]''', [http://robertsgroup.ecs.umass.edu/ Roberts Research Group] (Rohan Patil)

'''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon, [http://www.biochem.umass.edu/garman/index.html Garman Research Group]

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

'''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Rotello lab (Daniel Moyano-Marino)

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

'''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Thai lab (Rami Rajasekar Reddy)

'''[[Molecular_Playground/ERMan1]]''', Johan Sunryd

'''[[Molecular Playground/Insulin]]''', [http://robertsgroup.ecs.umass.edu/ Roberts Research Group] (Whitney Stoppel)

'''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia ([http://www.chem.umass.edu/~cmartin/ Martin] lab)

'''[[Molecular Playground/Human PPCA]]''', Nilima Kolli ([http://www.biochem.umass.edu/garman/index.html Garman Lab])

'''[[Molecular Playground/Alginate]]''', Bhatia Research Group (David Griffin)

'''[[Molecular Playground/Glutamate Receptor]]''', [http://chamberslab.com/wp/ Chambers Lab] (Amanda Hussey, Steve McCarron, Rosie Combs-Bachmann, Mariel Feliciano)

'''[[Molecular Playground/Biotin binding avidin]]''', Diego Amado (Thai Lab)

'''[[Molecular Playground/FIH]]''', Knapp Lab, (Cornelius Taabazuing, Breanne Holmes, John Hangasky)

'''[[User:Jiaming Zhuang|Molecular Playground/MMP12]]''', Thai lab (Jiaming Zhuang)

'''[[Molecular Playground/Pancreatic Lipase]]''', [http://www.umass.edu/rotellogroup/ Rotello lab] (Rui Tang)

'''[[Molecular Playground/Trypsin]]''', Thai-Vachet lab (Murage, Gladys)

'''[[Molecular playground/beta 2 microglobulin]]''', Vachet lab (Nick)

''' [[User:Jing Guo|Molecular Playground/Gluconase]]''', Thai lab (Jing Guo)

'''[[Molecular playground/Chymotrypsin]]''', Rotello lab (Brad)

'''[[CRABP I ( Cellular Retinoic Acid Binding Protein )|Molecular Playground/CRABP I]]''', [http://people.chem.umass.edu/gieraschlab/ Gierasch Lab] (Kristine Faye Pobre, Mylene Ferrolino,Mangai Periasamy)

'''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Knapp lab (Cristina Martin)

'''[[Molecular Playground/Glutathione Reductase]]''', Thai Lab (Reuben Chacko)

'''[[Molecular Playground/Velaglucerase]]''', Adriana Kita, Kaltashov Lab

'''[[Molecular Playground/Caspases]]''', Hardy Lab (Daniel Seeman)

'''[[Molecular Playground/Caspase-9 Regulation]]''', Hardy Lab (Kristen Huber)

Instructions:

'''We plan to award a prize for the best CBI Molecules page and/or scene!'''

Choose a molecule that is part of your research project.

1. If you don't already have one, request a Proteopedia account and log in. If you are new to Proteopedia, click Help in the navigation box on the left to get started.

2. Make yourself a sandbox page in which you will develop your CBI Molecule scene and description (Enter "User:your name/sandbox 1" (omit quotes) in the search box, then follow instructions to edit this page. See example [[User:Lynmarie K Thompson/Sandbox 1]]).

3. Follow the format of the sample CBI molecule page [[Molecular Playground/Bacterial Chemotaxis Receptors]]. Easiest way to do this is to copy this page (in editing mode), paste it into your sandbox page, keep the first paragraph about CBI molecules, and then edit to describe and display your molecule. Your goal is to make this an interesting, nontechnical description of the molecule. If multiple people in one group work on the same molecule, you can each make different scenes for the same CBI molecule and each describe them on the same proteopedia page. Talk with each other about your plans so you are not duplicating efforts.

4. Create an attractive scene for your molecule: use the scene authoring tools in the edit mode to create the view you like, then copy the wiki text into your window.

5. Follow instructions at [[Molecular Playground/Procedures]] as well. But don't "capture the state script for your scene"; that will be done for you (see #7). With your chosen Jmol scene for the Molecular Playground, specify a "banner", which will be projected with the molecule on the Molecular Playground. This should be a short, one-line headline for your scene that includes the name of the molecule and what is important about the scene or the molecule. Remember to design this for the general public, including non-scientists. My example is: "Molecular Playground banner: A bacterial chemotaxis receptor protein used by bacteria to "smell" their environment."

6. When you are happy with your sandbox page, make yourself a permanent Proteopedia page, which will be editable by others. Enter "Molecular Playground/your molecule" (omit quotes) in the search box, then follow the instructions to create a new page with this title. Copy the content of your sandbox to this new page.

7. When you have finished the final version of your page and scene, edit this CBI Molecules page to add a listing and link for your molecule, following the "Bacterial chemotaxis receptors" example above. Please list your lab group, with your name in parentheses. That way more than one name can be associated with a Molecular Playground page (if there are several students on the Molecular Playground page, please indicate your scene with your initials). It would be great to link the lab names to web pages too. Once this link is there, your scene is considered done, and someone will capture the state script for display on the Molecular Playground.

User:Kristen Huber/Sandbox 1

2010-05-04T19:08:16Z

Kristen Huber:

User:Kristen Huber/Sandbox 1

2010-05-04T19:06:31Z

Kristen Huber:

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

Caspase-9 belongs to a family of "molecular scissors" called cysteine aspartate proteases. These proteases are the facilitators of apoptosis, the highly process of programmed cell death which is an important cellular process critical for normal development and stability of an organism.

Caspase-9 is regulated by controlling its multimeric state through monomer-dimer transitions. Caspase-9 exists as an inactive monomer and becomes active upon dimerization. It is in this dimeric state that caspase-9 can “cut” its intended protein partners (called substrates) at a specific amino acid sequence. X-linked inhibitors of apoptosis proteins, specifically the BIR3 domain, bind to monomeric caspase-9 to block dimerization thus preventing activation.

==Structure==

<applet load='1jxq' size='400' color='white' frame='true' align='right' caption='Caspase-9 Dimer'

scene='User:Kristen_Huber/Sandbox_1/Caspase-9_dimer/1'>Caspase-9 Molecular Playground</applet>

<scene name='User:Kristen_Huber/Sandbox_1/Caspase-9_dimer/1'>Caspase-9 Molecular Playground</scene>

Molecular Playground banner: Cleaved Caspase-9, the active dimer.

Caspase-9 in the active, “prepared to cut” state, exists as a dimer. The dimer can be described as two monomers of a large and small subunit related by two-fold symmetry. The dimer is formed through interactions of the amino acids on a β-strand from each monomer which forms a continuous central β –sheet [1]. In addition, a seven residue loop also makes interactions across the interface. A loop bundle exists in this molecule as well and when properly ordered, it is able to “bind and cut” its substrate.

==Caspase-9/XIAP-BIR3 Interaction==

<applet load='1nw9' size='400' color='white' frame='true' align='right' caption='Caspase-9/XIAP-BIR3 Inhibitory Complex'

scene='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/1'>Caspase-9/XIAP BIR3 Molecular Playground</applet>

<scene name='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/1'>Caspase-9/XIAP BIR3 Molecular Playground</scene>

Molecular Playground banner: Caspase-9/XIAP BIR3 Complex, the inactive monomer.

The protein-protein interface of the Caspase-9/XIAP BIR3 complex is dominated by a high level of shape complimentarily, a large collection of van der Walls contacts, and 11 intermolecular hydrogen bonds scattered throughout the entire 2200 Å2 interface of the complex [2]. This interaction prevents caspase-9 from dimerizing as well as prevents the organization of the loop bundle thus making the molecule inactive.

==See Also==

* http://www.pdb.org/pdb/explore/explore.do?structureId=1JXQ Cleaved Caspase-9 Dimer ( PDB ID ; 1JXQ) at RCSB PDB]
* http://www.pdb.org/pdb/explore/explore.do?structureId=1NW9 Caspase-9/XIAP BIR3 Inhibitory Complex ( PDB ID ; 1NW9) at RCSB PDB]

==References==
*[1] Renatus, M.; Stennicke, H. R.; Scott, F. L.; Liddington, R. C.; Salvesen, G. S., Dimer formation drives the activation of the cell death protease caspase 9. PNAS 2001, 98, (25), 14250.
*[2] Shiozaki, E. N.; Chai, J.; Rigotti, D. J.; Riedl, S. J.; Li, P.; Srinivasula, S. M.; Alnemri, E. S.; Fairman, R.; Shi, Y., Mechanism of XIAP-mediated inhibition of caspase-9. Molecular Cell 2003, 11, (2), 519-527.

User:Kristen Huber/Sandbox 1

2010-05-04T19:02:15Z

Kristen Huber:

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

Caspase-9 belongs to a family of "molecular scissors" called cysteine aspartate proteases. These proteases are the facilitators of apoptosis, the highly process of programmed cell death which is an important cellular process critical for normal development and stability of an organism.

Caspase-9 is regulated by controlling its multimeric state through monomer-dimer transitions. Caspase-9 exists as an inactive monomer and becomes active upon dimerization. It is in this dimeric state that caspase-9 can “cut” its intended protein partners (called substrates) at a specific amino acid sequence. X-linked inhibitors of apoptosis proteins, specifically the BIR3 domain, bind to monomeric caspase-9 to block dimerization thus preventing activation.

==Structure==

<applet load='1jxq' size='400' color='white' frame='true' align='right' caption='Caspase-9 Dimer'

scene='User:Kristen_Huber/Sandbox_1/Caspase-9_dimer/1'>Caspase-9 Molecular Playground</scene>

<scene name='User:Kristen_Huber/Sandbox_1/Caspase-9_dimer/1'>Caspase-9 Molecular Playground</scene>

Molecular Playground banner: Cleaved Caspase-9, the active dimer.

Caspase-9 in the active, “prepared to cut” state, exists as a dimer. The dimer can be described as two monomers of a large and small subunit related by two-fold symmetry. The dimer is formed through interactions of the amino acids on a β-strand from each monomer which forms a continuous central β –sheet [1]. In addition, a seven residue loop also makes interactions across the interface. A loop bundle exists in this molecule as well and when properly ordered, it is able to “bind and cut” its substrate.

==Caspase-9/XIAP-BIR3 Interaction==

<applet load='1nw9' size='400' color='white' frame='true' align='right' caption='Caspase-9/XIAP-BIR3 Inhibitory Complex'

<scene='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/1'>Caspase-9/XIAP BIR3 Molecular Playground</scene>

<scene name='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/1'>Caspase-9/XIAP BIR3 Molecular Playground</scene>

The protein-protein interface of the Caspase-9/XIAP BIR3 complex is dominated by a high level of shape complimentarily, a large collection of van der Walls contacts, and 11 intermolecular hydrogen bonds scattered throughout the entire 2200 Å2 interface of the complex [2]. This interaction prevents caspase-9 from dimerizing as well as prevents the organization of the loop bundle thus making the molecule inactive.

==See Also==

* http://www.pdb.org/pdb/explore/explore.do?structureId=1JXQ Cleaved Caspase-9 Dimer ( PDB ID ; 1JXQ) at RCSB PDB]
* http://www.pdb.org/pdb/explore/explore.do?structureId=1NW9 Caspase-9/XIAP BIR3 Inhibitory Complex ( PDB ID ; 1NW9) at RCSB PDB]

==References==
*[1] Renatus, M.; Stennicke, H. R.; Scott, F. L.; Liddington, R. C.; Salvesen, G. S., Dimer formation drives the activation of the cell death protease caspase 9. PNAS 2001, 98, (25), 14250.
*[2] Shiozaki, E. N.; Chai, J.; Rigotti, D. J.; Riedl, S. J.; Li, P.; Srinivasula, S. M.; Alnemri, E. S.; Fairman, R.; Shi, Y., Mechanism of XIAP-mediated inhibition of caspase-9. Molecular Cell 2003, 11, (2), 519-527.

User:Kristen Huber/Sandbox 1

2010-05-04T19:01:37Z

Kristen Huber:

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

Caspase-9 belongs to a family of "molecular scissors" called cysteine aspartate proteases. These proteases are the facilitators of apoptosis, the highly process of programmed cell death which is an important cellular process critical for normal development and stability of an organism.

Caspase-9 is regulated by controlling its multimeric state through monomer-dimer transitions. Caspase-9 exists as an inactive monomer and becomes active upon dimerization. It is in this dimeric state that caspase-9 can “cut” its intended protein partners (called substrates) at a specific amino acid sequence. X-linked inhibitors of apoptosis proteins, specifically the BIR3 domain, bind to monomeric caspase-9 to block dimerization thus preventing activation.

==Structure==

<applet load='1jxq' size='400' color='white' frame='true' align='right' caption='Caspase-9 Dimer'

<scene='User:Kristen_Huber/Sandbox_1/Caspase-9_dimer/1'>Caspase-9 Molecular Playground</scene>

<scene name='User:Kristen_Huber/Sandbox_1/Caspase-9_dimer/1'>Caspase-9 Molecular Playground</scene>

Molecular Playground banner: Cleaved Caspase-9, the active dimer.

Caspase-9 in the active, “prepared to cut” state, exists as a dimer. The dimer can be described as two monomers of a large and small subunit related by two-fold symmetry. The dimer is formed through interactions of the amino acids on a β-strand from each monomer which forms a continuous central β –sheet [1]. In addition, a seven residue loop also makes interactions across the interface. A loop bundle exists in this molecule as well and when properly ordered, it is able to “bind and cut” its substrate.

==Caspase-9/XIAP-BIR3 Interaction==

<applet load='1nw9' size='400' color='white' frame='true' align='right' caption='Caspase-9/XIAP-BIR3 Inhibitory Complex'

<scene='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/1'>Caspase-9/XIAP BIR3 Molecular Playground</scene>

<scene name='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/1'>Caspase-9/XIAP BIR3 Molecular Playground</scene>

The protein-protein interface of the Caspase-9/XIAP BIR3 complex is dominated by a high level of shape complimentarily, a large collection of van der Walls contacts, and 11 intermolecular hydrogen bonds scattered throughout the entire 2200 Å2 interface of the complex [2]. This interaction prevents caspase-9 from dimerizing as well as prevents the organization of the loop bundle thus making the molecule inactive.

==See Also==

* http://www.pdb.org/pdb/explore/explore.do?structureId=1JXQ Cleaved Caspase-9 Dimer ( PDB ID ; 1JXQ) at RCSB PDB]
* http://www.pdb.org/pdb/explore/explore.do?structureId=1NW9 Caspase-9/XIAP BIR3 Inhibitory Complex ( PDB ID ; 1NW9) at RCSB PDB]

==References==
*[1] Renatus, M.; Stennicke, H. R.; Scott, F. L.; Liddington, R. C.; Salvesen, G. S., Dimer formation drives the activation of the cell death protease caspase 9. PNAS 2001, 98, (25), 14250.
*[2] Shiozaki, E. N.; Chai, J.; Rigotti, D. J.; Riedl, S. J.; Li, P.; Srinivasula, S. M.; Alnemri, E. S.; Fairman, R.; Shi, Y., Mechanism of XIAP-mediated inhibition of caspase-9. Molecular Cell 2003, 11, (2), 519-527.

User:Kristen Huber/Sandbox 1

2010-05-04T18:37:44Z

Kristen Huber:

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

Caspase-9 belongs to a family of "molecular scissors" called cysteine aspartate proteases. These proteases are the facilitators of apoptosis, the highly process of programmed cell death which is an important cellular process critical for normal development and stability of an organism.

Caspase-9 is regulated by controlling its multimeric state through monomer-dimer transitions. Caspase-9 exists as an inactive monomer and becomes active upon dimerization. It is in this dimeric state that caspase-9 can “cut” its intended protein partners (called substrates) at a specific amino acid sequence. X-linked inhibitors of apoptosis proteins, specifically the BIR3 domain, bind to monomeric caspase-9 to block dimerization thus preventing activation.

==Structure==

Molecular Playground banner: Cleaved Caspase-9, the active dimer.

Caspase-9 in the active, “prepared to cut” state, exists as a dimer. The dimer can be described as two monomers of a large and small subunit related by two-fold symmetry. The dimer is formed through interactions of the amino acids on a β-strand from each monomer which forms a continuous central β –sheet [1]. In addition, a seven residue loop also makes interactions across the interface. A loop bundle exists in this molecule as well and when properly ordered, it is able to “bind and cut” its substrate.

==Caspase-9/XIAP-BIR3 Interaction==

<applet load='1nw9' size='400' color='white' frame='true' align='right' caption='Caspase-9/XIAP-BIR3 Inhibitory Complex'

scene='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/1'>Caspase-9/XIAP BIR3 Molecular Playground</scene>

<scene name='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/1'>Caspase-9/XIAP BIR3 Molecular Playground</scene>

The protein-protein interface of the Caspase-9/XIAP BIR3 complex is dominated by a high level of shape complimentarily, a large collection of van der Walls contacts, and 11 intermolecular hydrogen bonds scattered throughout the entire 2200 Å2 interface of the complex [2]. This interaction prevents caspase-9 from dimerizing as well as prevents the organization of the loop bundle thus making the molecule inactive.

==See Also==

* http://www.pdb.org/pdb/explore/explore.do?structureId=1JXQ Cleaved Caspase-9 Dimer ( PDB ID ; 1JXQ) at RCSB PDB]
* http://www.pdb.org/pdb/explore/explore.do?structureId=1NW9 Caspase-9/XIAP BIR3 Inhibitory Complex ( PDB ID ; 1NW9) at RCSB PDB]

==References==
*[1] Renatus, M.; Stennicke, H. R.; Scott, F. L.; Liddington, R. C.; Salvesen, G. S., Dimer formation drives the activation of the cell death protease caspase 9. PNAS 2001, 98, (25), 14250.
*[2] Shiozaki, E. N.; Chai, J.; Rigotti, D. J.; Riedl, S. J.; Li, P.; Srinivasula, S. M.; Alnemri, E. S.; Fairman, R.; Shi, Y., Mechanism of XIAP-mediated inhibition of caspase-9. Molecular Cell 2003, 11, (2), 519-527.

User:Kristen Huber/Sandbox 1

2010-05-04T18:33:03Z

Kristen Huber:

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

Caspase-9 belongs to a family of "molecular scissors" called cysteine aspartate proteases. These proteases are the facilitators of apoptosis, the highly process of programmed cell death which is an important cellular process critical for normal development and stability of an organism.

Caspase-9 is regulated by controlling its multimeric state through monomer-dimer transitions. Caspase-9 exists as an inactive monomer and becomes active upon dimerization. It is in this dimeric state that caspase-9 can “cut” its intended protein partners (called substrates) at a specific amino acid sequence. X-linked inhibitors of apoptosis proteins, specifically the BIR3 domain, bind to monomeric caspase-9 to block dimerization thus preventing activation.

==Structure==

Molecular Playground banner: Cleaved Caspase-9, the active dimer.

Caspase-9 in the active, “prepared to cut” state, exists as a dimer. The dimer can be described as two monomers of a large and small subunit related by two-fold symmetry. The dimer is formed through interactions of the amino acids on a β-strand from each monomer which forms a continuous central β –sheet [1]. In addition, a seven residue loop also makes interactions across the interface. A loop bundle exists in this molecule as well and when properly ordered, it is able to “bind and cut” its substrate.

==Caspase-9/XIAP-BIR3 Interaction==

<applet load='1nw9' size='300' frame='true' align='right' caption='Caspase-9 Dimer'scene='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/1'>Molecular Playground banner: Caspase-9/XIAP BIR-3 Inhibitory Complex, the inactive monomer.</scene>/>

The protein-protein interface of the Caspase-9/XIAP BIR3 complex is dominated by a high level of shape complimentarily, a large collection of van der Walls contacts, and 11 intermolecular hydrogen bonds scattered throughout the entire 2200 Å2 interface of the complex [2]. This interaction prevents caspase-9 from dimerizing as well as prevents the organization of the loop bundle thus making the molecule inactive.

==See Also==

* http://www.pdb.org/pdb/explore/explore.do?structureId=1JXQ Cleaved Caspase-9 Dimer ( PDB ID ; 1JXQ) at RCSB PDB]
* http://www.pdb.org/pdb/explore/explore.do?structureId=1NW9 Caspase-9/XIAP BIR3 Inhibitory Complex ( PDB ID ; 1NW9) at RCSB PDB]

==References==
*[1] Renatus, M.; Stennicke, H. R.; Scott, F. L.; Liddington, R. C.; Salvesen, G. S., Dimer formation drives the activation of the cell death protease caspase 9. PNAS 2001, 98, (25), 14250.
*[2] Shiozaki, E. N.; Chai, J.; Rigotti, D. J.; Riedl, S. J.; Li, P.; Srinivasula, S. M.; Alnemri, E. S.; Fairman, R.; Shi, Y., Mechanism of XIAP-mediated inhibition of caspase-9. Molecular Cell 2003, 11, (2), 519-527.

User:Kristen Huber/Sandbox 1

2010-05-04T18:12:26Z

Kristen Huber:

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

Caspase-9 belongs to a family of "molecular scissors" called cysteine aspartate proteases. These proteases are the facilitators of apoptosis, the highly process of programmed cell death which is an important cellular process critical for normal development and stability of an organism.

Caspase-9 is regulated by controlling its multimeric state through monomer-dimer transitions. Caspase-9 exists as an inactive monomer and becomes active upon dimerization. It is in this dimeric state that caspase-9 can “cut” its intended protein partners (called substrates) at a specific amino acid sequence. X-linked inhibitors of apoptosis proteins, specifically the BIR3 domain, bind to monomeric caspase-9 to block dimerization thus preventing activation.

==Structure==

Molecular Playground banner: Cleaved Caspase-9, the active dimer.

Caspase-9 in the active, “prepared to cut” state, exists as a dimer. The dimer can be described as two monomers of a large and small subunit related by two-fold symmetry. The dimer is formed through interactions of the amino acids on a β-strand from each monomer which forms a continuous central β –sheet [1]. In addition, a seven residue loop also makes interactions across the interface. A loop bundle exists in this molecule as well and when properly ordered, it is able to “bind and cut” its substrate.

==Caspase-9/XIAP-BIR3 Interaction==

Molecular Playground banner: Caspase-9/XIAP BIR-3 Inhibitory Complex, the inactive monomer.

The protein-protein interface of the Caspase-9/XIAP BIR3 complex is dominated by a high level of shape complimentarily, a large collection of van der Walls contacts, and 11 intermolecular hydrogen bonds scattered throughout the entire 2200 Å2 interface of the complex [2]. This interaction prevents caspase-9 from dimerizing as well as prevents the organization of the loop bundle thus making the molecule inactive.

==See Also==

* http://www.pdb.org/pdb/explore/explore.do?structureId=1JXQ Cleaved Caspase-9 Dimer ( PDB ID ; 1JXQ) at RCSB PDB]
* http://www.pdb.org/pdb/explore/explore.do?structureId=1NW9 Caspase-9/XIAP BIR3 Inhibitory Complex ( PDB ID ; 1NW9) at RCSB PDB]

==References==
*[1] Renatus, M.; Stennicke, H. R.; Scott, F. L.; Liddington, R. C.; Salvesen, G. S., Dimer formation drives the activation of the cell death protease caspase 9. PNAS 2001, 98, (25), 14250.
*[2] Shiozaki, E. N.; Chai, J.; Rigotti, D. J.; Riedl, S. J.; Li, P.; Srinivasula, S. M.; Alnemri, E. S.; Fairman, R.; Shi, Y., Mechanism of XIAP-mediated inhibition of caspase-9. Molecular Cell 2003, 11, (2), 519-527.

User:Kristen Huber/Sandbox 1

2010-05-04T18:11:47Z

Kristen Huber:

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

Caspase-9 belongs to a family of "molecular scissors" called cysteine aspartate proteases. These proteases are the facilitators of apoptosis, the highly process of programmed cell death which is an important cellular process critical for normal development and stability of an organism.

Caspase-9 is regulated by controlling its multimeric state through monomer-dimer transitions. Caspase-9 exists as an inactive monomer and becomes active upon dimerization. It is in this dimeric state that caspase-9 can “cut” its intended protein partners (called substrates) at a specific amino acid sequence. X-linked inhibitors of apoptosis proteins, specifically the BIR3 domain, bind to monomeric caspase-9 to block dimerization thus preventing activation.

==Structure==

Molecular Playground banner: Cleaved Caspase-9, the active dimer.

Caspase-9 in the active, “prepared to cut” state, exists as a dimer. The dimer can be described as two monomers of a large and small subunit related by two-fold symmetry. The dimer is formed through interactions of the amino acids on a β-strand from each monomer which forms a continuous central β –sheet [1]. In addition, a seven residue loop also makes interactions across the interface. A loop bundle exists in this molecule as well and when properly ordered, it is able to “bind and cut” its substrate.

==Caspase-9/XIAP-BIR3 Interaction==

Molecular Playground banner: Caspase-9/XIAP BIR-3 Inhibitory Complex, the inactive monomer.

The protein-protein interface of the Caspase-9/XIAP BIR3 complex is dominated by a high level of shape complimentarily, a large collection of van der Walls contacts, and 11 intermolecular hydrogen bonds scattered throughout the entire 2200 Å2 interface of the complex [2]. This interaction prevents caspase-9 from dimerizing as well as prevents the organization of the loop bundle thus making the molecule inactive.

<scene name='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/2'>TextToBeDisplayed</scene>

==See Also==

* http://www.pdb.org/pdb/explore/explore.do?structureId=1JXQ Cleaved Caspase-9 Dimer ( PDB ID ; 1JXQ) at RCSB PDB]
* http://www.pdb.org/pdb/explore/explore.do?structureId=1NW9 Caspase-9/XIAP BIR3 Inhibitory Complex ( PDB ID ; 1NW9) at RCSB PDB]

==References==
*[1] Renatus, M.; Stennicke, H. R.; Scott, F. L.; Liddington, R. C.; Salvesen, G. S., Dimer formation drives the activation of the cell death protease caspase 9. PNAS 2001, 98, (25), 14250.
*[2] Shiozaki, E. N.; Chai, J.; Rigotti, D. J.; Riedl, S. J.; Li, P.; Srinivasula, S. M.; Alnemri, E. S.; Fairman, R.; Shi, Y., Mechanism of XIAP-mediated inhibition of caspase-9. Molecular Cell 2003, 11, (2), 519-527.

User:Kristen Huber/Sandbox 1

2010-05-04T18:06:58Z

Kristen Huber: /* Caspase-9/XIAP-BIR3 Interaction */

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

<applet load='1nw9' size='400' color='white' frame='true' align='right' caption='Caspase-9/XIAP BIR3(Inactive Monomer)'

Molecular Playground banner: Caspase-9/XIAP BIR-3 Inhibitory Complex, the inactive monomer.

Caspase-9 belongs to a family of "molecular scissors" called cysteine aspartate proteases. These proteases are the facilitators of apoptosis, the highly process of programmed cell death which is an important cellular process critical for normal development and stability of an organism.

Caspase-9 is regulated by controlling its multimeric state through monomer-dimer transitions. Caspase-9 exists as an inactive monomer and becomes active upon dimerization. It is in this dimeric state that caspase-9 can “cut” its intended protein partners (called substrates) at a specific amino acid sequence. X-linked inhibitors of apoptosis proteins, specifically the BIR3 domain, bind to monomeric caspase-9 to block dimerization thus preventing activation.

==Structure==

Caspase-9 in the active, “prepared to cut” state, exists as a dimer. The dimer can be described as two monomers of a large and small subunit related by two-fold symmetry. The dimer is formed through interactions of the amino acids on a β-strand from each monomer which forms a continuous central β –sheet [1]. In addition, a seven residue loop also makes interactions across the interface. A loop bundle exists in this molecule as well and when properly ordered, it is able to “bind and cut” its substrate.

==Caspase-9/XIAP-BIR3 Interaction==

The protein-protein interface of the Caspase-9/XIAP BIR3 complex is dominated by a high level of shape complimentarily, a large collection of van der Walls contacts, and 11 intermolecular hydrogen bonds scattered throughout the entire 2200 Å2 interface of the complex [2]. This interaction prevents caspase-9 from dimerizing as well as prevents the organization of the loop bundle thus making the molecule inactive.

<scene name='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/2'>TextToBeDisplayed</scene>

==See Also==

* http://www.pdb.org/pdb/explore/explore.do?structureId=1JXQ Cleaved Caspase-9 Dimer ( PDB ID ; 1JXQ) at RCSB PDB]
* http://www.pdb.org/pdb/explore/explore.do?structureId=1NW9 Caspase-9/XIAP BIR3 Inhibitory Complex ( PDB ID ; 1NW9) at RCSB PDB]

==References==
*[1] Renatus, M.; Stennicke, H. R.; Scott, F. L.; Liddington, R. C.; Salvesen, G. S., Dimer formation drives the activation of the cell death protease caspase 9. PNAS 2001, 98, (25), 14250.
*[2] Shiozaki, E. N.; Chai, J.; Rigotti, D. J.; Riedl, S. J.; Li, P.; Srinivasula, S. M.; Alnemri, E. S.; Fairman, R.; Shi, Y., Mechanism of XIAP-mediated inhibition of caspase-9. Molecular Cell 2003, 11, (2), 519-527.

User:Kristen Huber/Sandbox 1

2010-05-04T18:06:16Z

Kristen Huber:

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

<applet load='1nw9' size='400' color='white' frame='true' align='right' caption='Caspase-9/XIAP BIR3(Inactive Monomer)'

Molecular Playground banner: Caspase-9/XIAP BIR-3 Inhibitory Complex, the inactive monomer.

Caspase-9 belongs to a family of "molecular scissors" called cysteine aspartate proteases. These proteases are the facilitators of apoptosis, the highly process of programmed cell death which is an important cellular process critical for normal development and stability of an organism.

Caspase-9 is regulated by controlling its multimeric state through monomer-dimer transitions. Caspase-9 exists as an inactive monomer and becomes active upon dimerization. It is in this dimeric state that caspase-9 can “cut” its intended protein partners (called substrates) at a specific amino acid sequence. X-linked inhibitors of apoptosis proteins, specifically the BIR3 domain, bind to monomeric caspase-9 to block dimerization thus preventing activation.

==Structure==

Caspase-9 in the active, “prepared to cut” state, exists as a dimer. The dimer can be described as two monomers of a large and small subunit related by two-fold symmetry. The dimer is formed through interactions of the amino acids on a β-strand from each monomer which forms a continuous central β –sheet [1]. In addition, a seven residue loop also makes interactions across the interface. A loop bundle exists in this molecule as well and when properly ordered, it is able to “bind and cut” its substrate.

==Caspase-9/XIAP-BIR3 Interaction==

The protein-protein interface of the Caspase-9/XIAP BIR3 complex is dominated by a high level of shape complimentarily, a large collection of van der Walls contacts, and 11 intermolecular hydrogen bonds scattered throughout the entire 2200 Å2 interface of the complex [2]. This interaction prevents caspase-9 from dimerizing as well as prevents the organization of the loop bundle thus making the molecule inactive.

==See Also==

* http://www.pdb.org/pdb/explore/explore.do?structureId=1JXQ Cleaved Caspase-9 Dimer ( PDB ID ; 1JXQ) at RCSB PDB]
* http://www.pdb.org/pdb/explore/explore.do?structureId=1NW9 Caspase-9/XIAP BIR3 Inhibitory Complex ( PDB ID ; 1NW9) at RCSB PDB]

==References==
*[1] Renatus, M.; Stennicke, H. R.; Scott, F. L.; Liddington, R. C.; Salvesen, G. S., Dimer formation drives the activation of the cell death protease caspase 9. PNAS 2001, 98, (25), 14250.
*[2] Shiozaki, E. N.; Chai, J.; Rigotti, D. J.; Riedl, S. J.; Li, P.; Srinivasula, S. M.; Alnemri, E. S.; Fairman, R.; Shi, Y., Mechanism of XIAP-mediated inhibition of caspase-9. Molecular Cell 2003, 11, (2), 519-527.

User:Kristen Huber/Sandbox 1

2010-05-04T18:00:04Z

Kristen Huber:

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

<applet load='1nw9' size='400' color='white' frame='true' align='right' caption='Caspase-9/XIAP BIR3(Inactive Monomer)'

Molecular Playground banner: Caspase-9/XIAP BIR-3 Inhibitory Complex, the inactive monomer.

Caspase-9 belongs to a family of "molecular scissors" called cysteine aspartate proteases. These proteases are the facilitators of apoptosis, the highly process of programmed cell death which is an important cellular process critical for normal development and stability of an organism.

Caspase-9 is regulated by controlling its multimeric state through monomer-dimer transitions. Caspase-9 exists as an inactive monomer and becomes active upon dimerization. It is in this dimeric state that caspase-9 can “cut” its intended protein partners (called substrates) at a specific amino acid sequence. X-linked inhibitors of apoptosis proteins, specifically the BIR3 domain, bind to monomeric caspase-9 to block dimerization thus preventing activation.

==Structure==

Caspase-9 in the active, “prepared to cut” state, exists as a dimer. The dimer can be described as two monomers of a large and small subunit related by two-fold symmetry. The dimer is formed through interactions of the amino acids on a β-strand from each monomer which forms a continuous central β –sheet [1]. In addition, a seven residue loop also makes interactions across the interface. A loop bundle exists in this molecule as well and when properly ordered, it is able to “bind and cut” its substrate.

==Caspase-9/XIAP-BIR3 Interaction==

<scene name='User:Kristen_Huber/Sandbox_1/Caspase-9_xiap_bir3_complex/1'>TextToBeDisplayed</scene>

The protein-protein interface of the Caspase-9/XIAP BIR3 complex is dominated by a high level of shape complimentarily, a large collection of van der Walls contacts, and 11 intermolecular hydrogen bonds scattered throughout the entire 2200 Å2 interface of the complex [2]. This interaction prevents caspase-9 from dimerizing as well as prevents the organization of the loop bundle thus making the molecule inactive.

==See Also==

* http://www.pdb.org/pdb/explore/explore.do?structureId=1JXQ Cleaved Caspase-9 Dimer ( PDB ID ; 1JXQ) at RCSB PDB]
* http://www.pdb.org/pdb/explore/explore.do?structureId=1NW9 Caspase-9/XIAP BIR3 Inhibitory Complex ( PDB ID ; 1NW9) at RCSB PDB]

==References==
*[1] Renatus, M.; Stennicke, H. R.; Scott, F. L.; Liddington, R. C.; Salvesen, G. S., Dimer formation drives the activation of the cell death protease caspase 9. PNAS 2001, 98, (25), 14250.
*[2] Shiozaki, E. N.; Chai, J.; Rigotti, D. J.; Riedl, S. J.; Li, P.; Srinivasula, S. M.; Alnemri, E. S.; Fairman, R.; Shi, Y., Mechanism of XIAP-mediated inhibition of caspase-9. Molecular Cell 2003, 11, (2), 519-527.

User:Kristen Huber/Sandbox 1

2010-05-04T17:18:56Z

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

<applet load='1jxq' size='400' color='white' frame='true' align='right' caption='Dimeric Caspase-9 (Active)'

Molecular Playground banner: Cleaved Caspase-9, the active dimer.

<applet load='1nw9' size='400' color='white' frame='true' align='right' caption='Caspase-9/XIAP BIR3(Inactive Monomer)'

Molecular Playground banner: Caspase-9/XIAP BIR-3 Inhibitory Complex, the inactive monomer.

Caspase-9 belongs to a family of "molecular scissors" called cysteine aspartate proteases. These proteases are the facilitators of apoptosis, the highly process of programmed cell death which is an important cellular process critical for normal development and stability of an organism.

Caspase-9 is regulated by controlling its multimeric state through monomer-dimer transitions. Caspase-9 exists as an inactive monomer and becomes active upon dimerization. It is in this dimeric state that caspase-9 can “cut” its intended protein partners (called substrates) at a specific amino acid sequence. X-linked inhibitors of apoptosis proteins, specifically the BIR3 domain, bind to monomeric caspase-9 to block dimerization thus preventing activation.

==Structure==

Caspase-9 in the active, “prepared to cut” state, exists as a dimer. The dimer can be described as two monomers of a large and small subunit related by two-fold symmetry. The dimer is formed through interactions of the amino acids on a β-strand from each monomer which forms a continuous central β –sheet [1]. In addition, a seven residue loop also makes interactions across the interface. A loop bundle exists in this molecule as well and when properly ordered, it is able to “bind and cut” its substrate.

==Caspase-9/XIAP-BIR3 Interaction==

The protein-protein interface of the Caspase-9/XIAP BIR3 complex is dominated by a high level of shape complimentarily, a large collection of van der Walls contacts, and 11 intermolecular hydrogen bonds scattered throughout the entire 2200 Å2 interface of the complex [2]. This interaction prevents caspase-9 from dimerizing as well as prevents the organization of the loop bundle thus making the molecule inactive.

==See Also==

* http://www.pdb.org/pdb/explore/explore.do?structureId=1JXQ Cleaved Caspase-9 Dimer ( PDB ID ; 1JXQ) at RCSB PDB]
* http://www.pdb.org/pdb/explore/explore.do?structureId=1NW9 Caspase-9/XIAP BIR3 Inhibitory Complex ( PDB ID ; 1NW9) at RCSB PDB]

==References==
*[1] Renatus, M.; Stennicke, H. R.; Scott, F. L.; Liddington, R. C.; Salvesen, G. S., Dimer formation drives the activation of the cell death protease caspase 9. PNAS 2001, 98, (25), 14250.
*[2] Shiozaki, E. N.; Chai, J.; Rigotti, D. J.; Riedl, S. J.; Li, P.; Srinivasula, S. M.; Alnemri, E. S.; Fairman, R.; Shi, Y., Mechanism of XIAP-mediated inhibition of caspase-9. Molecular Cell 2003, 11, (2), 519-527.