1evq

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THE CRYSTAL STRUCTURE OF THE THERMOPHILIC CARBOXYLESTERASE EST2 FROM ALICYCLOBACILLUS ACIDOCALDARIUS

File:1evq.gif


1evq, resolution 2.6Å

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OverviewOverview

EST2 is a novel thermophilic carboxylesterase, isolated and cloned from, Alicyclobacillus (formerly Bacillus) acidocaldarius, which optimally, hydrolyses esters with acyl chain lengths of six to eight carbon atoms at, 70 degrees C. On the basis of the amino acid sequence homology, it has, been classified as a member of the mammalian hormone-sensitive lipase, (HSL) subfamily.The crystal structure of EST2, complexed with a sulphonyl, derivative, has been determined at 2.6 A resolution by a multiple, wavelength anomalous diffraction experiment on a seleno-methionine, derivative. EST2 presents a canonical alpha/beta hydrolase core, shielded, at the C-terminal side by a cap region built up of five helices. It, contains the lipase-like catalytic triad, Ser155, His282 and Asp252, whereby the nucleophile is covalently modified. This allows an unambiguous, view of the putative active site of EST2, detecting the oxyanion hole, in, whose formation the amino acid sequence motif His81-Gly82-Gly83-Gly84 is, involved, and the hydrophobic binding pocket for the acyl chain. The, structural model here reported provides the first example of a transition, state analogue of an esterase/lipase belonging to the HSL group, thus, affording useful information for the design of medical inhibitors., Moreover, as the first X-ray structure of a thermophilic carboxylesterase, the comparison with its mesophilic homologue, the Brefeldin A esterase, (BFAE) from Bacillus subtilis, allows the identification of putative, determinants of thermal stability.

About this StructureAbout this Structure

1EVQ is a Single protein structure of sequence from Alicyclobacillus acidocaldarius with EPE and TRS as ligands. Active as Carboxylesterase, with EC number 3.1.1.1 Full crystallographic information is available from OCA.

ReferenceReference

A snapshot of a transition state analogue of a novel thermophilic esterase belonging to the subfamily of mammalian hormone-sensitive lipase., De Simone G, Galdiero S, Manco G, Lang D, Rossi M, Pedone C, J Mol Biol. 2000 Nov 10;303(5):761-71. PMID:11061974

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