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| [[Image:1f57.jpg|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1f57| PDB=1f57 | SCENE= }} | | {{STRUCTURE_1f57| PDB=1f57 | SCENE= }} |
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| '''CARBOXYPEPTIDASE A COMPLEX WITH D-CYSTEINE AT 1.75 A'''
| | ===CARBOXYPEPTIDASE A COMPLEX WITH D-CYSTEINE AT 1.75 A=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_10955996}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 10955996 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_10955996}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[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 Fri May 2 15:54:54 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 02:42:53 2008'' |
