2OEG

Open and Closed Structures of the UDP-Glucose Pyrophosphorylase from Leishmania major

2OEG の概要

• エントリーDOI: 10.2210/pdb2oeg/pdb
• 関連するPDBエントリー: 2OEF
• 分子名称: UTP-glucose-1-phosphate uridylyltransferase 2, putative, URIDINE-5'-DIPHOSPHATE-GLUCOSE (3 entities in total)
• 機能のキーワード: rossmann-fold, beta-helix, pyrophosphorylase, transferase
• 由来する生物種: Leishmania major
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57512.09

構造登録者

Steiner, T. (登録日: 2006-12-29, 公開日: 2007-02-13, 最終更新日: 2023-12-27)

主引用文献

Steiner, T.,Lamerz, A.C.,Hess, P.,Breithaupt, C.,Krapp, S.,Bourenkov, G.,Huber, R.,Gerardy-Schahn, R.,Jacob, U.
Open and Closed Structures of the UDP-glucose Pyrophosphorylase from Leishmania major.
J.Biol.Chem., 282:13003-13010, 2007

PubMed Abstract: Uridine diphosphate-glucose pyrophosphorylase (UGPase) represents a ubiquitous enzyme, which catalyzes the formation of UDP-glucose, a key metabolite of the carbohydrate pathways of all organisms. In the protozoan parasite Leishmania major, which causes a broad spectrum of diseases and is transmitted to humans by sand fly vectors, UGPase represents a virulence factor because of its requirement for the synthesis of cell surface glycoconjugates. Here we present the crystal structures of the L. major UGPase in its uncomplexed apo form (open conformation) and in complex with UDP-glucose (closed conformation). The UGPase consists of three distinct domains. The N-terminal domain exhibits species-specific differences in length, which might permit distinct regulation mechanisms. The central catalytic domain resembles a Rossmann-fold and contains key residues that are conserved in many nucleotidyltransferases. The C-terminal domain forms a left-handed parallel beta-helix (LbetaH), which represents a rarely observed structural element. The presented structures together with mutagenesis analyses provide a basis for a detailed analysis of the catalytic mechanism and for the design of species-specific UGPase inhibitors.

PubMed: 17303565
DOI: 10.1074/jbc.M609984200

実験手法

X-RAY DIFFRACTION (2.3 Å)