From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:2qlb.jpg|left|200px]] | + | {{Seed}} |
| | + | [[Image:2qlb.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_2qlb| PDB=2qlb | SCENE= }} | | {{STRUCTURE_2qlb| PDB=2qlb | SCENE= }} |
| | | | |
| - | '''Crystal Structure of caspase-7 with inhibitor AC-ESMD-CHO'''
| + | ===Crystal Structure of caspase-7 with inhibitor AC-ESMD-CHO=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | Many protein substrates of caspases are cleaved at noncanonical sites in comparison to the recognition motifs reported for the three caspase subgroups. To provide insight into the specificity and aid in the design of drugs to control cell death, crystal structures of caspase-7 were determined in complexes with six peptide analogs (Ac-DMQD-Cho, Ac-DQMD-Cho, Ac-DNLD-Cho, Ac-IEPD-Cho, Ac-ESMD-Cho, Ac-WEHD-Cho) that span the major recognition motifs of the three subgroups. The crystal structures show that the S2 pocket of caspase-7 can accommodate diverse residues. Glu is not required at the P3 position because Ac-DMQD-Cho, Ac-DQMD-Cho and Ac-DNLD-Cho with varied P3 residues are almost as potent as the canonical Ac-DEVD-Cho. P4 Asp was present in the better inhibitors of caspase-7. However, the S4 pocket of executioner caspase-7 has alternate regions for binding of small branched aliphatic or polar residues similar to those of initiator caspase-8. The observed plasticity of the caspase subsites agrees very well with the reported cleavage of many proteins at noncanonical sites. The results imply that factors other than the P4-P1 sequence, such as exosites, contribute to the in vivo substrate specificity of caspases. The novel peptide binding site identified on the molecular surface of the current structures is suggested to be an exosite of caspase-7. These results should be considered in the design of selective small molecule inhibitors of this pharmacologically important protease.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17697120}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17697120 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_17697120}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 34: |
Line 38: |
| | [[Category: Thiol protease]] | | [[Category: Thiol protease]] |
| | [[Category: Zymogen]] | | [[Category: Zymogen]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:31:55 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:43:29 2008'' |
Revision as of 11:43, 28 July 2008
Template:STRUCTURE 2qlb
Crystal Structure of caspase-7 with inhibitor AC-ESMD-CHO
Template:ABSTRACT PUBMED 17697120
About this Structure
2QLB is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Plasticity of S2-S4 specificity pockets of executioner caspase-7 revealed by structural and kinetic analysis., Agniswamy J, Fang B, Weber IT, FEBS J. 2007 Sep;274(18):4752-65. Epub 2007 Aug 14. PMID:17697120
Page seeded by OCA on Mon Jul 28 14:43:29 2008
