1F57
CARBOXYPEPTIDASE A COMPLEX WITH D-CYSTEINE AT 1.75 A
Summary for 1F57
| Entry DOI | 10.2210/pdb1f57/pdb |
| Descriptor | CARBOXYPEPTIDASE A, ZINC ION, D-CYSTEINE, ... (4 entities in total) |
| Functional Keywords | metalloprotease inhibitor, hydrolase |
| Biological source | Bos taurus (cattle) |
| Cellular location | Secreted, extracellular space: P00730 |
| Total number of polymer chains | 1 |
| Total formula weight | 34631.99 |
| Authors | van Aalten, D.M.,Chong, C.R.,Joshua-Tor, L. (deposition date: 2000-06-13, release date: 2000-09-06, Last modification date: 2024-11-13) |
| Primary citation | van Aalten, D.M.,Chong, C.R.,Joshua-Tor, L. Crystal structure of carboxypeptidase A complexed with D-cysteine at 1.75 A - inhibitor-induced conformational changes. Biochemistry, 39:10082-10089, 2000 Cited by PubMed Abstract: 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. PubMed: 10955996DOI: 10.1021/bi000952h PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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