1MX9

Crystal Structure of Human Liver Carboxylesterase in complexed with naloxone methiodide, a heroin analogue

Summary for 1MX9

• Entry DOI: 10.2210/pdb1mx9/pdb
• Related: 1MX1 1MX5
• Descriptor: liver Carboxylesterase I, 2-acetamido-2-deoxy-beta-D-glucopyranose, (5A,17R)-4,5-EPOXY-3,14-DIHYDROXY-17-METHYL-6-OXO-17-(2-PROPENYL)-MORPHINANIUM, ... (4 entities in total)
• Functional Keywords: esterase, hydrolase, heroin
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 12
• Total formula weight: 733120.55

Authors

Bencharit, S.,Morton, C.L.,Xue, Y.,Potter, P.M.,Redinbo, M.R. (deposition date: 2002-10-01, release date: 2003-04-08, Last modification date: 2024-10-16)

Primary citation

Bencharit, S.,Morton, C.L.,Xue, Y.,Potter, P.M.,Redinbo, M.R.
Structural Basis of Heroin and Cocaine Metabolism by a Promiscuous Human Drug-Processing Enzyme
Nat.Struct.Biol., 10:349-356, 2003

PubMed Abstract: 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.

PubMed: 12679808
DOI: 10.1038/nsb919

Experimental method

X-RAY DIFFRACTION (2.9 Å)