2P98

E. coli methionine aminopeptidase monometalated with inhibitor YE7

2P98 の概要

• エントリーDOI: 10.2210/pdb2p98/pdb
• 関連するPDBエントリー: 2GTX
• 分子名称: Methionine aminopeptidase, MANGANESE (II) ION, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: monometalated, mononuclear, mn(ii)-form, hydrolase, enzyme-inhibitor complex, metalloenzyme
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29414.69

構造登録者

Ye, Q. (登録日: 2007-03-24, 公開日: 2007-11-20, 最終更新日: 2024-02-21)

主引用文献

Huang, M.,Xie, S.X.,Ma, Z.Q.,Huang, Q.Q.,Nan, F.J.,Ye, Q.Z.
Inhibition of Monometalated Methionine Aminopeptidase: Inhibitor Discovery and Crystallographic Analysis.
J.Med.Chem., 50:5735-5742, 2007

PubMed Abstract: Two divalent metal ions are commonly seen in the active-site cavity of methionine aminopeptidase, and at least one of the metal ions is directly involved in catalysis. Although ample structural and functional information is available for dimetalated enzyme, methionine aminopeptidase likely functions as a monometalated enzyme under physiological conditions. Information on structure, as well as catalysis and inhibition, of the monometalated enzyme is lacking. By improving conditions of high-throughput screening, we identified a unique inhibitor with specificity toward the monometalated enzyme. Kinetic characterization indicates a mutual exclusivity in binding between the inhibitor and the second metal ion at the active site. This is confirmed by X-ray structure, and this inhibitor coordinates with the first metal ion and occupies the space normally occupied by the second metal ion. Kinetic and structural analyses of the inhibition by this and other inhibitors provide insight in designing effective inhibitors of methionine aminopeptidase.

PubMed: 17948983
DOI: 10.1021/jm700930k

実験手法

X-RAY DIFFRACTION (1.7 Å)