1uwt: Difference between revisions

Transition-state mimicry is increasingly important both to understand, enzyme mechanism and to direct the synthesis of putative therapeutic, agents. X-ray crystallography is able to provide vital information on the, interactions between an enzyme and the potential inhibitor. Here we report, the structures, at approximately 2 A resolution, of a family GH1, beta-glycosidase from the hyperthermophilic archaeon Sulfolobus, solfataricus, in complex with both covalently (derived from, 2-fluoro-glycosides) and noncovalently (hydroximolactam) bound inhibitors., The enzyme has broad specificity, accommodating both gluco- and, galacto-configured substrates, and the crystallographic data demonstrate, that the only difference in the way these ligands bind lies in the, interactions between Gln18, Glu432, and Trp433, and the hydroxyl group at, the O3 and O4 positions. Inhibition by the differently configured ligands, was also shown to be extremely similar, with K(i) values of 1.04 and 1.08, microM for the gluco and galacto epimers, respectively. The noncovalently, bound inhibitors have a trigonal anomeric carbon, adopt a (4)H(3), (half-chair) conformation, and an interaction is formed between O2 and the, catalytic nucleophile, all of which contribute to (partial) mimicry of the, oxocarbenium-ion-like transition state. The inhibition of the, beta-glycosidase from S. solfataricus by hydroximolactams is discussed in, light of the emerging work on family GH1 glycosidase inhibition by a, spectrum of putative transition-state mimics.

1UWT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sulfolobus_solfataricus Sulfolobus solfataricus] with ACT and GTL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Beta-galactosidase Beta-galactosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.23 3.2.1.23] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UWT OCA].  

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