1naw

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spinqualitylabelsall models 1naw, resolution 2.0Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

ENOLPYRUVYL TRANSFERASE

Overview

BACKGROUND. The ever increasing number of antibiotic resistant bacteria, has fuelled interest in the development of new antibiotics and other, antibacterial agents. The major structural element of the bacterial cell, wall is the heteropolymer peptidoglycan and the enzymes of peptidoglycan, biosynthesis are potential targets for antibacterial agents. One such, enzyme is UDP-N-acetylglucosamine enolpyruvyltransferase (EPT) which, catalyzes the first committed step in peptidoglycan biosynthesis: the, transfer of the enolpyruvyl moiety of phosphoenolpyruvate (PEP) to the, 3-hydroxyl of UDP-N-acetylglucosamine (UDPGlcNAc). EPT is of potential, pharmaceutical interest because it is inhibited by the broad spectrum, antibiotic fosfomycin. RESULTS. The crystal structure of substrate-free, EPT has been determined at 2.0 A resolution. The structure reveals a, two-domain protein with an unusual fold (inside out alpha/beta barrel), which is built up from the sixfold repetition of one folding unit. The, only repetitive element in the amino acid sequence is a short motif, Leu-X3-Gly(Ala), which is responsible for the formation of hydrogen-bond, interactions between the folding units. An enzyme which catalyzes a, similar reaction to EPT, 5-enolpyruvylshikimate-3-phosphate synthase, (EPSPS), has a very similar structure despite an amino acid sequence, identity of only 25%. To date, only these two enzymes appear to display, this characteristic fold. CONCLUSIONS. The present structure reflects the, open conformation of the enzyme which is probably stabilized through two, residues, a lysine and an arginine, located in the cleft between the, domains. Binding of the negatively charged UDPGlcNAc to these residues, could neutralize the repulsive force between the two domains, thereby, allowing the movement of a catalytically active cysteine residue towards, the cleft.

About this Structure

1NAW is a Single protein structure of sequence from Enterobacter cloacae with HAI as ligand. Active as UDP-N-acetylglucosamine 1-carboxyvinyltransferase, with EC number 2.5.1.7 Full crystallographic information is available from OCA.

Reference

Crystal structure of UDP-N-acetylglucosamine enolpyruvyltransferase, the target of the antibiotic fosfomycin., Schonbrunn E, Sack S, Eschenburg S, Perrakis A, Krekel F, Amrhein N, Mandelkow E, Structure. 1996 Sep 15;4(9):1065-75. PMID:8805592

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