3O9M

Co-crystallization studies of full length recombinant BChE with cocaine offers insights into cocaine detoxification

PDB DOI: https://doi.org/10.2210/pdb3O9M/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Cricetulus griseus
Mutation(s): No

Deposited: 2010-08-04 Released: 2011-04-13
Deposition Author(s): Asojo, O.A., Ngamelue, M.N., Homma, K., Lockridge, O.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.98 Å
R-Value Free: 0.262
R-Value Work: 0.223
R-Value Observed: 0.225

wwPDB Validation 3D Report Full Report

This is version 1.1 of the entry. See complete history.

Literature

Cocrystallization studies of full-length recombinant butyrylcholinesterase (BChE) with cocaine.

Asojo, O.A., Ngamelue, M.N., Homma, K., Lockridge, O.

(2011) Acta Crystallogr Sect F Struct Biol Cryst Commun 67: 434-437

PubMed: 21505234 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1107/S1744309111004805
Primary Citation of Related Structures:
3O9M

PubMed Abstract:
Human butyrylcholinesterase (BChE; EC 3.1.1.8) is a 340 kDa tetrameric glycoprotein that is present in human serum at about 5 mg l(-1) and has well documented therapeutic effects on cocaine toxicity. BChE holds promise as a therapeutic that reduces and finally eliminates the rewarding effects of cocaine, thus weaning an addict from the drug. There have been extensive computational studies of cocaine hydrolysis by BChE. Since there are no reported structures of BChE with cocaine or any of the hydrolysis products, full-length monomeric recombinant wild-type BChE was cocrystallized with cocaine. The refined 3 Å resolution structure appears to retain the hydrolysis product benzoic acid in sufficient proximity to form a hydrogen bond to the active-site Ser198.

Organizational Affiliation

Pathology and Microbiology Department, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198-6495, USA. oasojo@unmc.edu

Macromolecule Content

Total Structure Weight: 130.54 kDa
Atom Count: 8,472
Modelled Residue Count: 1,062
Deposited Residue Count: 1,148
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Cholinesterase	A, B	574	Homo sapiens	Mutation(s): 0 Gene Names: BCHE, CHE1 EC: 3.1.1.8
UniProt & NIH Common Fund Data Resources
Find proteins for P06276 (Homo sapiens) Explore P06276 Go to UniProtKB: P06276
PHAROS: P06276 GTEx: ENSG00000114200
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P06276
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
BEZ Query on BEZ Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth B]	C [auth A], D [auth B]	BENZOIC ACID C₇ H₆ O₂ WPYMKLBDIGXBTP-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain D [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth B]