1JU4

BACTERIAL COCAINE ESTERASE COMPLEX WITH PRODUCT

Summary for 1JU4

• Entry DOI: 10.2210/pdb1ju4/pdb
• Related: 1JU3
• Descriptor: cocaine esterase, BENZOIC ACID (3 entities in total)
• Functional Keywords: alpha/beta hydrolase, hydrolase
• Biological source: Rhodococcus sp. MB1
• Cellular location: Cytoplasm : Q9L9D7
• Total number of polymer chains: 1
• Total formula weight: 63473.76

Authors

Larsen, N.A.,Turner, J.M.,Stevens, J.,Rosser, S.J.,Basran, A.,Lerner, R.A.,Bruce, N.C.,Wilson, I.A. (deposition date: 2001-08-23, release date: 2001-12-21, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.63 Å)