1JU3

BACTERIAL COCAINE ESTERASE COMPLEX WITH TRANSITION STATE ANALOG

1JU3 の概要

• エントリーDOI: 10.2210/pdb1ju3/pdb
• 関連するPDBエントリー: 1JU4
• 分子名称: cocaine esterase, PHENYL BORONIC ACID (3 entities in total)
• 機能のキーワード: alpha/beta hydrolase, hydrolase
• 由来する生物種: Rhodococcus sp. MB1
• 細胞内の位置: Cytoplasm : Q9L9D7
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 63473.57

構造登録者

Larsen, N.A.,Turner, J.M.,Stevens, J.,Rosser, S.J.,Basran, A.,Lerner, R.A.,Bruce, N.C.,Wilson, I.A. (登録日: 2001-08-23, 公開日: 2001-12-21, 最終更新日: 2024-10-16)

主引用文献

Larsen, N.A.,Turner, J.M.,Stevens, J.,Rosser, S.J.,Basran, A.,Lerner, R.A.,Bruce, N.C.,Wilson, I.A.
Crystal structure of a bacterial cocaine esterase.
Nat.Struct.Biol., 9:17-21, 2002

PubMed Abstract: Here we report the first structure of a cocaine-degrading enzyme. The bacterial esterase, cocE, hydrolyzes pharmacologically active (-)-cocaine to a non-psychoactive metabolite with a rate faster than any other reported cocaine esterase (kcat = 7.8 s-1 and KM = 640 nM). Because of the high catalytic proficiency of cocE, it is an attractive candidate for novel protein-based therapies for cocaine overdose. The crystal structure of cocE, solved by multiple anomalous dispersion (MAD) methods, reveals that cocE is a serine esterase composed of three domains: (i) a canonical alpha/beta hydrolase fold (ii) an alpha-helical domain that caps the active site and (iii) a jelly-roll-like beta-domain that interacts extensively with the other two domains. The active site was identified within the interface of all three domains by analysis of the crystal structures of transition state analog adduct and product complexes, which were refined at 1.58 A and 1.63 A resolution, respectively. These structural studies suggest that substrate recognition arises partly from interactions between the benzoyl moiety of cocaine and a highly evolved specificity pocket.

PubMed: 11742345
DOI: 10.1038/nsb742

実験手法

X-RAY DIFFRACTION (1.58 Å)