1ju3
From Proteopedia
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BACTERIAL COCAINE ESTERASE COMPLEX WITH TRANSITION STATE ANALOG
Overview
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.
About this Structure
1JU3 is a Single protein structure of sequence from Rhodococcus sp. mb1 with PBC as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of a bacterial cocaine esterase., Larsen NA, Turner JM, Stevens J, Rosser SJ, Basran A, Lerner RA, Bruce NC, Wilson IA, Nat Struct Biol. 2002 Jan;9(1):17-21. PMID:11742345
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