3KGQ

Carboxypeptidase A liganded to an organic small-molecule: conformational changes

3KGQ の概要

• エントリーDOI: 10.2210/pdb3kgq/pdb
• 分子名称: Carboxypeptidase A1, ZINC ION, SODIUM ION, ... (8 entities in total)
• 機能のキーワード: intestinal protease, zinc-metallocarboxypeptidase-citrate ternary complex, carboxypeptidase, hydrolase, metal-binding, metalloprotease
• 由来する生物種: Bos taurus (bovine)
• 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: 35823.05

構造登録者

Fernandez, D.,Boix, E.,Pallares, I.,Aviles, F.X.,Vendrell, J. (登録日: 2009-10-29, 公開日: 2010-10-27, 最終更新日: 2024-11-13)

主引用文献

Fernandez, D.,Boix, E.,Pallares, I.,Aviles, F.X.,Vendrell, J.
Structural and Functional Analysis of the Complex between Citrate and the Zinc Peptidase Carboxypeptidase A
Enzyme Res, 2011:128676-128676, 2011

PubMed Abstract: A high-resolution carboxypeptidase-Zn(2+)-citrate complex was studied by X-ray diffraction and enzyme kinetics for the first time. The citrate molecule acts as a competitive inhibitor of this benchmark zinc-dependent peptidase, chelating the catalytic zinc ion in the active site of the enzyme and inducing a conformational change such that carboxypeptidase adopts the conformation expected to occur by substrate binding. Citrate adopts an extended conformation with half of the molecule facing the zinc ion, while the other half is docked in the S1' hydrophobic specificity pocket of the enzyme, in contrast with the binding mode expected for a substrate like phenylalanine or a peptidomimetic inhibitor like benzylsuccinic acid. Combined structural and enzymatic analysis describes the characteristics of the binding of this ligand that, acting against physiologically relevant zinc-dependent proteases, may serve as a general model in the design of new drug-protecting molecules for the oral delivery of drugs of peptide origin.

PubMed: 21804935
DOI: 10.4061/2011/128676

実験手法

X-RAY DIFFRACTION (1.7 Å)