1mx5
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Crystal Structure of Human Liver Carboxylesterase in complexed with homatropine, a cocaine analogue
OverviewOverview
We present the first crystal structures of a human protein bound to, analogs of cocaine and heroin. Human carboxylesterase 1 (hCE1) is a, broad-spectrum bioscavenger that catalyzes the hydrolysis of heroin and, cocaine, and the detoxification of organophosphate chemical weapons, such, as sarin, soman and tabun. Crystal structures of the hCE1 glycoprotein in, complex with the cocaine analog homatropine and the heroin analog naloxone, provide explicit details about narcotic metabolism in humans. The hCE1, active site contains both specific and promiscuous compartments, which, enable the enzyme to act on structurally distinct chemicals. A selective, surface ligand-binding site regulates the trimer-hexamer equilibrium of, hCE1 and allows each hCE1 monomer to bind two narcotic molecules, simultaneously. The bioscavenger properties of hCE1 can likely be used to, treat both narcotic overdose and chemical weapon exposure.
DiseaseDisease
Known disease associated with this structure: Monocyte carboxylesterase deficiency (1) OMIM:[114835]
About this StructureAbout this Structure
1MX5 is a Single protein structure of sequence from Homo sapiens with NAG, NDG, SIA, CL and HTQ as ligands. Active as Carboxylesterase, with EC number 3.1.1.1 Full crystallographic information is available from OCA.
ReferenceReference
Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme., Bencharit S, Morton CL, Xue Y, Potter PM, Redinbo MR, Nat Struct Biol. 2003 May;10(5):349-56. PMID:12679808
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