2OEF

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

Summary for 2OEF

• Entry DOI: 10.2210/pdb2oef/pdb
• Descriptor: UTP-glucose-1-phosphate uridylyltransferase 2, putative, SULFATE ION (3 entities in total)
• Functional Keywords: rossmann-fold, beta-helix, pyrophosphorylase, transferase
• Biological source: Leishmania major
• Total number of polymer chains: 1
• Total formula weight: 57137.91

Authors

Steiner, T. (deposition date: 2006-12-29, release date: 2007-02-13, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)