2ql9: Difference between revisions
New page: left|200px<br /> <applet load="2ql9" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ql9, resolution 2.14Å" /> '''Crystal Structure o... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2ql9. | [[Image:2ql9.jpg|left|200px]]<br /><applet load="2ql9" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2ql9" size=" | |||
caption="2ql9, resolution 2.14Å" /> | caption="2ql9, resolution 2.14Å" /> | ||
'''Crystal Structure of Caspase-7 with inhibitor AC-DQMD-CHO'''<br /> | '''Crystal Structure of Caspase-7 with inhibitor AC-DQMD-CHO'''<br /> | ||
| Line 8: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
2QL9 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ACE and CIT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22 3.4.22] Full crystallographic information is available from [http:// | 2QL9 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ACE:'>ACE</scene> and <scene name='pdbligand=CIT:'>CIT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22 3.4.22] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QL9 OCA]. | ||
==Reference== | ==Reference== | ||
| Line 29: | Line 28: | ||
[[Category: zymogen]] | [[Category: zymogen]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:58:22 2008'' | ||
Revision as of 13:58, 23 January 2008
|
Crystal Structure of Caspase-7 with inhibitor AC-DQMD-CHO
OverviewOverview
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.
About this StructureAbout this Structure
2QL9 is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Hydrolase, with EC number 3.4.22 Full crystallographic information is available from OCA.
ReferenceReference
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 Aug 14;. PMID:17697120
Page seeded by OCA on Wed Jan 23 12:58:22 2008