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Structural basis of UDP-galactose binding by α-1,3-galactosyltransferase (α3GT) : role of negative charge on aspartic acid 316 in structure and activity

Tumbale, Percy and Jamaluddin, Haryati and Thiyagarajan, Nethaji and Brew, Keith and Acharya, K. Ravi (2008) Structural basis of UDP-galactose binding by α-1,3-galactosyltransferase (α3GT) : role of negative charge on aspartic acid 316 in structure and activity. Biochemistry, 47 (33). pp. 8711-8718.

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Official URL: http://dx.doi.org/10.1021/bi800852a

Abstract

α-1,3-Galactosyltransferase (α3GT) catalyzes the transfer of galactose from UDP-galactose to form an α 1−3 link with β-linked galactosides; it is part of a family of homologous retaining glycosyltransferases that includes the histo-blood group A and B glycosyltransferases, Forssman glycolipid synthase, iGb3 synthase, and some uncharacterized prokaryotic glycosyltransferases. In mammals, the presence or absence of active forms of these enzymes results in antigenic differences between individuals and species that modulate the interplay between the immune system and pathogens. The catalytic mechanism of α3GT is controversial, but the structure of an enzyme complex with the donor substrate could illuminate both this and the basis of donor substrate specificity. We report here the structure of the complex of a low-activity mutant α3GT with UDP-galactose (UDP-gal) exhibiting a bent configuration stabilized by interactions of the galactose with multiple residues in the enzyme including those in a highly conserved region (His315 to Ser318). Analysis of the properties of mutants containing substitutions for these residues shows that catalytic activity is strongly affected by His315 and Asp316. The negative charge of Asp316 is crucial for catalytic activity, and structural studies of two mutants show that its interaction with Arg202 is needed for an active site structure that facilitates the binding of UDP-gal in a catalytically competent conformation.

Item Type:Article
Uncontrolled Keywords:glycoconjugates, UDP-galactose
Subjects:Q Science > QH Natural history > QH301 Biology
Divisions:Science
ID Code:6897
Deposited By: Ms Zalinda Shuratman
Deposited On:20 Nov 2008 07:09
Last Modified:20 Nov 2008 07:17

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