4ARF

CRYSTAL STRUCTURE OF THE PEPTIDASE DOMAIN OF COLLAGENASE H FROM CLOSTRIDIUM HISTOLYTICUM IN COMPLEX WITH THE PEPTIDIC INHIBITOR ISOAMYLPHOSPHONYL-GLY-PRO-ALA AT 1.77 ANGSTROM RESOLUTION.

4ARF の概要

• エントリーDOI: 10.2210/pdb4arf/pdb
• 関連するPDBエントリー: 4AR1
• 分子名称: COLH PROTEIN, ISOAMYLPHOSPHONYL-GLY-PRO-ALA, ZINC ION, ... (5 entities in total)
• 機能のキーワード: hydrolase-inhibitor complex, collagenolysis, hydrolyse, metalloprotease, hexxh, hydrolase/inhibitor
• 由来する生物種: CLOSTRIDIUM HISTOLYTICUM; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46373.66

構造登録者

Eckhard, U.,Brandstetter, H. (登録日: 2012-04-23, 公開日: 2013-06-05, 最終更新日: 2024-11-13)

主引用文献

Eckhard, U.,Schonauer, E.,Brandstetter, H.
Structural Basis for Activity Regulation and Substrate Preference of Clostridial Collagenases G, H, and T.
J.Biol.Chem., 288:20184-, 2013

PubMed Abstract: Clostridial collagenases are among the most efficient enzymes to degrade by far the most predominant protein in the biosphere. Here we present crystal structures of the peptidases of three clostridial collagenase isoforms (ColG, ColH, and ColT). The comparison of unliganded and liganded structures reveals a quaternary subdomain dynamics. In the unliganded ColH structure, this globular dynamics is modulated by an aspartate switch motion that binds to the catalytic zinc. We further identified a calcium binding site in proximity to the catalytic zinc. Both ions are required for full activity, explaining why calcium critically affects the enzymatic activity of clostridial collagenases. Our studies further reveal that loops close to the active site thus serve as characteristic substrate selectivity filter. These elements explain the distinct peptidolytic and collagenolytic activities of these enzymes and provide a rational framework to engineer collagenases with customized substrate specificity as well as for inhibitor design.

PubMed: 23703618
DOI: 10.1074/JBC.M112.448548

実験手法

X-RAY DIFFRACTION (1.77 Å)