1f57: Difference between revisions
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|PDB= 1f57 |SIZE=350|CAPTION= <scene name='initialview01'>1f57</scene>, resolution 1.75Å | |PDB= 1f57 |SIZE=350|CAPTION= <scene name='initialview01'>1f57</scene>, resolution 1.75Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=DCY:D-CYSTEINE'>DCY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Carboxypeptidase_A Carboxypeptidase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.1 3.4.17.1] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Carboxypeptidase_A Carboxypeptidase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.1 3.4.17.1] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1f57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f57 OCA], [http://www.ebi.ac.uk/pdbsum/1f57 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1f57 RCSB]</span> | |||
}} | }} | ||
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[[Category: Chong, C R.]] | [[Category: Chong, C R.]] | ||
[[Category: Joshua-Tor, L.]] | [[Category: Joshua-Tor, L.]] | ||
[[Category: metalloprotease inhibitor]] | [[Category: metalloprotease inhibitor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:16:09 2008'' | ||
Revision as of 20:16, 30 March 2008
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| , resolution 1.75Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Carboxypeptidase A, with EC number 3.4.17.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CARBOXYPEPTIDASE A COMPLEX WITH D-CYSTEINE AT 1.75 A
OverviewOverview
D-Cysteine differs from the antiarthritis drug D-penicillamine by only two methyl groups on the beta-carbon yet inhibits carboxypeptidase A (CPD) by a distinct mechanism: D-cysteine binds tightly to the active site zinc, while D-penicillamine catalyzes metal removal. To investigate the structural basis for this difference, we solved the crystal structure of carboxypeptidase A complexed with D-cysteine (D-Cys) at 1.75-A resolution. D-Cys binds the active site zinc with a sulfur ligand and forms additional interactions with surrounding side chains of the enzyme. The structure explains the difference in potency between D-Cys and L-Cys and provides insight into the mechanism of D-penicillamine inhibition. D-Cys binding induces a concerted motion of the side chains around the zinc ion, similar to that found in other carboxypeptidase-inhibitor crystal structures and along a limited path. Analysis of concerted motions of CPD and CPD-inhibitor crystal structures reveals a clustering of these structures into distinct groups. Using the restricted conformational flexibility of a drug target in this type of analysis could greatly enhance efficiency in drug design.
About this StructureAbout this Structure
1F57 is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of carboxypeptidase A complexed with D-cysteine at 1.75 A - inhibitor-induced conformational changes., van Aalten DM, Chong CR, Joshua-Tor L, Biochemistry. 2000 Aug 22;39(33):10082-9. PMID:10955996
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