2h48
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2h48.gif|left|200px]] | [[Image:2h48.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2h48", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | + | --> | |
| - | + | {{STRUCTURE_2h48| PDB=2h48 | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystal structure of human caspase-1 (Cys362->Ala, Cys364->Ala, Cys397->Ala) in complex with 3-[2-(2-benzyloxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-4-oxo-pentanoic acid (z-VAD-FMK)''' | '''Crystal structure of human caspase-1 (Cys362->Ala, Cys364->Ala, Cys397->Ala) in complex with 3-[2-(2-benzyloxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-4-oxo-pentanoic acid (z-VAD-FMK)''' | ||
| Line 29: | Line 26: | ||
[[Category: Scheer, J M.]] | [[Category: Scheer, J M.]] | ||
[[Category: Wells, J A.]] | [[Category: Wells, J A.]] | ||
| - | [[Category: | + | [[Category: Allosteric side]] |
| - | [[Category: | + | [[Category: Caspase-1]] |
| - | [[Category: | + | [[Category: Z-vad-fmk]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:50:55 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 02:50, 4 May 2008
Crystal structure of human caspase-1 (Cys362->Ala, Cys364->Ala, Cys397->Ala) in complex with 3-[2-(2-benzyloxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-4-oxo-pentanoic acid (z-VAD-FMK)
Overview
We present a common allosteric mechanism for control of inflammatory and apoptotic caspases. Highly specific thiol-containing inhibitors of the human inflammatory caspase-1 were identified by using disulfide trapping, a method for site-directed small-molecule discovery. These compounds became trapped by forming a disulfide bond with a cysteine residue in the cavity at the dimer interface approximately 15 A away from the active site. Mutational and structural analysis uncovered a linear circuit of functional residues that runs from one active site through the allosteric cavity and into the second active site. Kinetic analysis revealed robust positive cooperativity not seen in other endopeptidases. Recently, disulfide trapping identified a similar small-molecule site and allosteric transition in the apoptotic caspase-7 that shares only a 23% sequence identity with caspase-1. Together, these studies show a general small-molecule-binding site for functionally reversing the zymogen activation of caspases and suggest a common regulatory site for the allosteric control of inflammation and apoptosis.
About this Structure
2H48 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A common allosteric site and mechanism in caspases., Scheer JM, Romanowski MJ, Wells JA, Proc Natl Acad Sci U S A. 2006 May 16;103(20):7595-600. Epub 2006 May 8. PMID:16682620 Page seeded by OCA on Sun May 4 05:50:55 2008
