1F57

CARBOXYPEPTIDASE A COMPLEX WITH D-CYSTEINE AT 1.75 A

1F57 の概要

• エントリーDOI: 10.2210/pdb1f57/pdb
• 分子名称: CARBOXYPEPTIDASE A, ZINC ION, D-CYSTEINE, ... (4 entities in total)
• 機能のキーワード: metalloprotease inhibitor, hydrolase
• 由来する生物種: Bos taurus (cattle)
• 細胞内の位置: Secreted, extracellular space: P00730
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34631.99

構造登録者

van Aalten, D.M.,Chong, C.R.,Joshua-Tor, L. (登録日: 2000-06-13, 公開日: 2000-09-06, 最終更新日: 2024-11-13)

主引用文献

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

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: 10955996
DOI: 10.1021/bi000952h

実験手法

X-RAY DIFFRACTION (1.75 Å)