2IXC

RmlC M. tuberculosis with dTDP-rhamnose

2IXC の概要

• エントリーDOI: 10.2210/pdb2ixc/pdb
• 関連するPDBエントリー: 1PM7 1UPI 2IXH 2IXI 2IXJ 2IXK 2IXL
• 分子名称: DTDP-4-DEHYDRORHAMNOSE 3,5-EPIMERASE RMLC, 2'-DEOXY-THYMIDINE-BETA-L-RHAMNOSE (3 entities in total)
• 機能のキーワード: isomerase, lipopolysaccharide biosynthesis, epimerise, epimerase, epimerize
• 由来する生物種: MYCOBACTERIUM TUBERCULOSIS
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 91541.12

構造登録者

Dong, C.,Naismith, J.H. (登録日: 2006-07-07, 公開日: 2006-10-26, 最終更新日: 2024-05-08)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.79 Å)