2DQY

Crystal structure of human carboxylesterase in complex with cholate and palmitate

Summary for 2DQY

• Entry DOI: 10.2210/pdb2dqy/pdb
• Related: 2DQZ 2DR0 2H7C
• Descriptor: Liver carboxylesterase 1, 2-acetamido-2-deoxy-beta-D-glucopyranose, N-acetyl-alpha-neuraminic acid, ... (7 entities in total)
• Functional Keywords: cholesterol metabolism, foam cells, macrophage, monocyte, atherosclerosis, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 3
• Total formula weight: 183525.38

Authors

Bencharit, S.,Edwards, C.C.,Morton, C.L.,Howard-Williams, E.L.,Potter, P.M.,Redinbo, M.R. (deposition date: 2006-06-02, release date: 2006-08-29, Last modification date: 2023-10-25)

Primary citation

Bencharit, S.,Edwards, C.C.,Morton, C.L.,Howard-Williams, E.L.,Kuhn, P.,Potter, P.M.,Redinbo, M.R.
Multisite promiscuity in the processing of endogenous substrates by human carboxylesterase 1
J.Mol.Biol., 363:201-214, 2006

PubMed Abstract: 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.

PubMed: 16962139
DOI: 10.1016/j.jmb.2006.08.025

Experimental method

X-RAY DIFFRACTION (3 Å)