2IXC

RmlC M. tuberculosis with dTDP-rhamnose

Summary for 2IXC

• Entry DOI: 10.2210/pdb2ixc/pdb
• Related: 1PM7 1UPI 2IXH 2IXI 2IXJ 2IXK 2IXL
• Descriptor: DTDP-4-DEHYDRORHAMNOSE 3,5-EPIMERASE RMLC, 2'-DEOXY-THYMIDINE-BETA-L-RHAMNOSE (3 entities in total)
• Functional Keywords: isomerase, lipopolysaccharide biosynthesis, epimerise, epimerase, epimerize
• Biological source: MYCOBACTERIUM TUBERCULOSIS
• Total number of polymer chains: 4
• Total formula weight: 91541.12

Authors

Dong, C.,Naismith, J.H. (deposition date: 2006-07-07, release date: 2006-10-26, Last modification date: 2024-05-08)

Primary citation

Dong, C.,Major, L.L.,Srikannathasan, V.,Errey, J.C.,Giraud, M.F.,Lam, J.S.,Graninger, M.,Messner, P.,Mcneil, M.R.,Field, R.A.,Whitfield, C.,Naismith, J.H.
Rmlc, a C3' and C5' Carbohydrate Epimerase, Appears to Operate Via an Intermediate with an Unusual Twist Boat Conformation.
J.Mol.Biol., 365:146-, 2007

PubMed Abstract: The striking feature of carbohydrates is their constitutional, conformational and configurational diversity. Biology has harnessed this diversity and manipulates carbohydrate residues in a variety of ways, one of which is epimerization. RmlC catalyzes the epimerization of the C3' and C5' positions of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4-hexulose. RmlC is the third enzyme of the rhamnose pathway, and represents a validated anti-bacterial drug target. Although several structures of the enzyme have been reported, the mechanism and the nature of the intermediates have remained obscure. Despite its relatively small size (22 kDa), RmlC catalyzes four stereospecific proton transfers and the substrate undergoes a major conformational change during the course of the transformation. Here we report the structure of RmlC from several organisms in complex with product and product mimics. We have probed site-directed mutants by assay and by deuterium exchange. The combination of structural and biochemical data has allowed us to assign key residues and identify the conformation of the carbohydrate during turnover. Clear knowledge of the chemical structure of RmlC reaction intermediates may offer new opportunities for rational drug design.

PubMed: 17046787
DOI: 10.1016/J.JMB.2006.09.063

Experimental method

X-RAY DIFFRACTION (1.79 Å)