1G1A

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

Summary for 1G1A

• Entry DOI: 10.2210/pdb1g1a/pdb
• Descriptor: DTDP-D-GLUCOSE 4,6-DEHYDRATASE, SULFATE ION, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• Functional Keywords: rossmann fold, protein-nad complex, short chain dehydrogenase, lyase
• Biological source: Salmonella enterica subsp. enterica serovar Typhimurium
• Total number of polymer chains: 4
• Total formula weight: 166588.33

Authors

Allard, S.T.M.,Giraud, M.-F.,Whitfield, C.,Graninger, M.,Messner, P.,Naismith, J.H. (deposition date: 2000-10-11, release date: 2001-03-21, Last modification date: 2024-02-07)

Primary citation

Allard, S.T.,Giraud, M.F.,Whitfield, C.,Graninger, M.,Messner, P.,Naismith, J.H.
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.
J.Mol.Biol., 307:283-295, 2001

PubMed Abstract: 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.

PubMed: 11243820
DOI: 10.1006/jmbi.2000.4470

Experimental method

X-RAY DIFFRACTION (2.47 Å)