2h7c

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Revision as of 20:21, 12 November 2007

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spinqualitylabelsall models 2h7c, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of human carboxylesterase in complex with Coenzyme A

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Human carboxylesterase 1 (hCE1) is a drug and endobiotic-processing serine, hydrolase that exhibits relatively broad substrate specificity. It has, been implicated in a variety of endogenous cholesterol metabolism pathways, including the following apparently disparate reactions: cholesterol ester, hydrolysis (CEH), fatty acyl Coenzyme A hydrolysis (FACoAH), acyl-Coenzyme, A:cholesterol acyltransfer (ACAT), and fatty acyl ethyl ester synthesis, (FAEES). The structural basis for the ability of hCE1 to perform these, catalytic actions involving large substrates and products has remained, unclear. Here we present four crystal structures of the hCE1 glycoprotein, in complexes with the following endogenous substrates or substrate, analogues: Coenzyme A, the fatty acid palmitate, and the bile acids, cholate and taurocholate. While the active site of hCE1 was known to be, promiscuous and capable of interacting with a variety of chemically, distinct ligands, these structures reveal that the enzyme contains two, additional ligand-binding sites and that each site also exhibits, relatively non-specific ligand-binding properties. Using this multisite, promiscuity, hCE1 appears structurally capable of assembling several, catalytic events depending, apparently, on the physiological state of the, cellular environment. These results expand our understanding of enzyme, promiscuity and indicate that, in the case of hCE1, multiple non-specific, sites are employed to perform distinct catalytic actions.

Disease

Known disease associated with this structure: Monocyte carboxylesterase deficiency (1) OMIM:[114835]

About this Structure

2H7C is a Single protein structure of sequence from Homo sapiens with NAG, NDG, SIA, SO4 and COA as ligands. Active as Carboxylesterase, with EC number 3.1.1.1 Full crystallographic information is available from OCA.

Reference

Multisite promiscuity in the processing of endogenous substrates by human carboxylesterase 1., Bencharit S, Edwards CC, Morton CL, Howard-Williams EL, Kuhn P, Potter PM, Redinbo MR, J Mol Biol. 2006 Oct 13;363(1):201-14. Epub 2006 Aug 15. PMID:16962139

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