1MX9: Crystal Structure Of Human Liver Carboxylesterase In Complexed With Naloxone Methiodide, A Heroin Analogue

Citation:
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.
PDB ID: 1MX9Download
MMDB ID: 22653
PDB Deposition Date: 2002/10/1
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 2.9  Å
Source Organism:
Similar Structures:
Biological Unit for 1MX9: hexameric; determined by author and by software (PISA)
Molecular Components in 1MX9
Label Count Molecule
Proteins (6 molecules)
6
Liver Carboxylesterase I(Gene symbol: CES1)
Molecule annotation
Chemicals (13 molecules)
1
7
2
6
* Click molecule labels to explore molecular sequence information.

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