2p2c
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | Specific and potent caspase inhibitors are indispensable for the | + | Specific and potent caspase inhibitors are indispensable for the dissection of the intricate pathways leading to apoptosis. We selected a designed ankyrin repeat protein (DARPin) from a combinatorial library that inhibits caspase-2 in vitro with a subnanomolar inhibition constant and, in contrast to the peptidic caspase inhibitors, with very high specificity for this particular caspase. The crystal structure of this inhibitor (AR_F8) in complex with caspase-2 reveals the molecular basis for the specificity and, together with kinetic analyses, the allosteric mechanism of inhibition. The structure also shows a conformation of the active site that can be exploited for the design of inhibitory compounds. AR_F8 is a specific inhibitor of an initiator caspase and has the potential to help identify the function of caspase-2 in the complex biological apoptotic signaling network. |
==About this Structure== | ==About this Structure== | ||
| Line 10: | Line 10: | ||
==Reference== | ==Reference== | ||
| - | Inhibition of | + | Inhibition of caspase-2 by a designed ankyrin repeat protein: specificity, structure, and inhibition mechanism., Schweizer A, Roschitzki-Voser H, Amstutz P, Briand C, Gulotti-Georgieva M, Prenosil E, Binz HK, Capitani G, Baici A, Pluckthun A, Grutter MG, Structure. 2007 May;15(5):625-36. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17502107 17502107] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Briand, C.]] | [[Category: Briand, C.]] | ||
[[Category: Capitani, G.]] | [[Category: Capitani, G.]] | ||
| - | [[Category: Gruetter, M | + | [[Category: Gruetter, M G.]] |
[[Category: Voser, HRoschitzki.]] | [[Category: Voser, HRoschitzki.]] | ||
[[Category: apoptosis]] | [[Category: apoptosis]] | ||
| Line 26: | Line 26: | ||
[[Category: ribosome display]] | [[Category: ribosome display]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:25:12 2008'' |
Revision as of 16:25, 21 February 2008
|
Inhibition of caspase-2 by a designed ankyrin repeat protein (DARPin)
Overview
Specific and potent caspase inhibitors are indispensable for the dissection of the intricate pathways leading to apoptosis. We selected a designed ankyrin repeat protein (DARPin) from a combinatorial library that inhibits caspase-2 in vitro with a subnanomolar inhibition constant and, in contrast to the peptidic caspase inhibitors, with very high specificity for this particular caspase. The crystal structure of this inhibitor (AR_F8) in complex with caspase-2 reveals the molecular basis for the specificity and, together with kinetic analyses, the allosteric mechanism of inhibition. The structure also shows a conformation of the active site that can be exploited for the design of inhibitory compounds. AR_F8 is a specific inhibitor of an initiator caspase and has the potential to help identify the function of caspase-2 in the complex biological apoptotic signaling network.
About this Structure
2P2C is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Inhibition of caspase-2 by a designed ankyrin repeat protein: specificity, structure, and inhibition mechanism., Schweizer A, Roschitzki-Voser H, Amstutz P, Briand C, Gulotti-Georgieva M, Prenosil E, Binz HK, Capitani G, Baici A, Pluckthun A, Grutter MG, Structure. 2007 May;15(5):625-36. PMID:17502107
Page seeded by OCA on Thu Feb 21 18:25:12 2008
