1ya4
From Proteopedia
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Crystal Structure of Human Liver Carboxylesterase 1 in complex with tamoxifen
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Overview
Human carboxylesterase 1 (hCE1) exhibits broad substrate specificity and, is involved in xenobiotic processing and endobiotic metabolism. We present, and analyze crystal structures of hCE1 in complexes with the, cholesterol-lowering drug mevastatin, the breast cancer drug tamoxifen, the fatty acyl ethyl ester (FAEE) analogue ethyl acetate, and the novel, hCE1 inhibitor benzil. We find that mevastatin does not appear to be a, substrate for hCE1, and instead acts as a partially non-competitive, inhibitor of the enzyme. Similarly, we show that tamoxifen is a low, micromolar, partially non-competitive inhibitor of hCE1. Further, we, describe the structural basis for the inhibition of hCE1 by the, nanomolar-affinity dione benzil, which acts by forming both covalent and, non-covalent complexes with the enzyme. Our results provide detailed, insights into the catalytic and non-catalytic processing of small, molecules by hCE1, and suggest that the efficacy of clinical drugs may be, modulated by targeted hCE1 inhibitors.
Disease
Known disease associated with this structure: Monocyte carboxylesterase deficiency (1) OMIM:[114835]
About this Structure
1YA4 is a Single protein structure of sequence from Homo sapiens with NAG, SIA, SO4 and CTX as ligands. Active as Carboxylesterase, with EC number 3.1.1.1 Full crystallographic information is available from OCA.
Reference
Structural insights into drug processing by human carboxylesterase 1: tamoxifen, mevastatin, and inhibition by benzil., Fleming CD, Bencharit S, Edwards CC, Hyatt JL, Tsurkan L, Bai F, Fraga C, Morton CL, Howard-Williams EL, Potter PM, Redinbo MR, J Mol Biol. 2005 Sep 9;352(1):165-77. PMID:16081098
Page seeded by OCA on Mon Nov 12 20:16:58 2007
