1g1a

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(New page: 200px<br /><applet load="1g1a" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g1a, resolution 2.47&Aring;" /> '''THE CRYSTAL STRUCTUR...)
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Revision as of 13:29, 20 November 2007


1g1a, resolution 2.47Å

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THE CRYSTAL STRUCTURE OF DTDP-D-GLUCOSE 4,6-DEHYDRATASE (RMLB)FROM SALMONELLA ENTERICA SEROVAR TYPHIMURIUM

Overview

l-Rhamnose is a 6-deoxyhexose that is found in a variety of different, glycoconjugates in the cell walls of pathogenic bacteria. The precursor of, l-rhamnose is dTDP-l-rhamnose, which is synthesised from glucose-, 1-phosphate and deoxythymidine triphosphate (dTTP) via a pathway requiring, four enzymes. Significantly this pathway does not exist in humans and all, four enzymes therefore represent potential therapeutic targets., dTDP-D-glucose 4,6-dehydratase (RmlB; EC 4.2.1.46) is the second enzyme in, the dTDP-L-rhamnose biosynthetic pathway. The structure of Salmonella, enterica serovar Typhimurium RmlB had been determined to 2.47 A resolution, with its cofactor NAD(+) bound. The structure has been refined to a, crystallographic R-factor of 20.4 % and an R-free value of 24.9 % with, good stereochemistry.RmlB functions as a homodimer with monomer, association occurring principally through hydrophobic interactions via a, four-helix bundle. Each monomer exhibits an alpha/beta structure that can, be divided into two domains. The larger N-terminal domain binds the, nucleotide cofactor NAD(+) and consists of a seven-stranded beta-sheet, surrounded by alpha-helices. The smaller C-terminal domain is responsible, for binding the sugar substrate dTDP-d-glucose and contains four, beta-strands and six alpha-helices. The two domains meet to form a cavity, in the enzyme. The highly conserved active site Tyr(167)XXXLys(171), catalytic couple and the GlyXGlyXXGly motif at the N terminus characterise, RmlB as a member of the short-chain dehydrogenase/reductase extended, family.The quaternary structure of RmlB and its similarity to a number of, other closely related short-chain dehydrogenase/reductase enzymes have, enabled us to propose a mechanism of catalysis for this important enzyme.

About this Structure

1G1A is a Single protein structure of sequence from Salmonella enterica with SO4 and NAD as ligands. Active as dTDP-glucose 4,6-dehydratase, with EC number 4.2.1.46 Full crystallographic information is available from OCA.

Reference

The crystal structure of dTDP-D-Glucose 4,6-dehydratase (RmlB) from Salmonella enterica serovar Typhimurium, the second enzyme in the dTDP-l-rhamnose pathway., Allard ST, Giraud MF, Whitfield C, Graninger M, Messner P, Naismith JH, J Mol Biol. 2001 Mar 16;307(1):283-95. PMID:11243820

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