1rhq: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1rhq.gif|left|200px]] | [[Image:1rhq.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1rhq", 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_1rhq| PDB=1rhq | SCENE= }} | |||
| | |||
}} | |||
'''CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A BROMOMETHOXYPHENYL INHIBITOR''' | '''CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A BROMOMETHOXYPHENYL INHIBITOR''' | ||
| Line 28: | Line 25: | ||
[[Category: Rotonda, J.]] | [[Category: Rotonda, J.]] | ||
[[Category: Soisson, S M.]] | [[Category: Soisson, S M.]] | ||
[[Category: | [[Category: Apopain]] | ||
[[Category: | [[Category: Caspase-3]] | ||
[[Category: | [[Category: Cpp32]] | ||
[[Category: Cysteine protease]] | |||
[[Category: | [[Category: Yama]] | ||
[[Category: | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:55:56 2008'' | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 13:55, 30 April 2008
CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A BROMOMETHOXYPHENYL INHIBITOR
OverviewOverview
Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. They are key agents in inflammation and apoptosis and are attractive targets for therapy against inflammation, neurodegeneration, ischemia, and cancer. Many caspase structures are known, but most involve either peptide or protein inhibitors, unattractive candidates for drug development. We present seven crystal structures of inhibited caspase-3 that illustrate several approaches to reducing the peptidyl characteristics of the inhibitors while maintaining their potency and selectivity. The inhibitors reduce the peptidyl nature of inhibitors while preserving binding potency by (1). exploiting a hydrophobic binding site C-terminal to the cleavage site, (2). replacing the negatively charged aspartyl residue at P4 with neutral groups, and (3). using a peptidomimetic 5,6,7-tricyclic system or a pyrazinone at P2-P3. In addition, we have found that two nicotinic acid aldehydes induce a significant conformational change in the S2 and S3 subsites of caspase-3, revealing an unexpected binding mode. These results advance the search for caspase-directed drugs by revealing how unacceptable molecular features can be removed without loss of potency.
About this StructureAbout this Structure
1RHQ is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Reducing the peptidyl features of caspase-3 inhibitors: a structural analysis., Becker JW, Rotonda J, Soisson SM, Aspiotis R, Bayly C, Francoeur S, Gallant M, Garcia-Calvo M, Giroux A, Grimm E, Han Y, McKay D, Nicholson DW, Peterson E, Renaud J, Roy S, Thornberry N, Zamboni R, J Med Chem. 2004 May 6;47(10):2466-74. PMID:15115390 Page seeded by OCA on Wed Apr 30 13:55:56 2008