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UDP-N-acetylglucosamine enolpyruvyltransferase (EPT or MurA) catalyzes the first
committed step in the biosynthesis of the bacterial cell wall. Since it does not occur in
mammals, it is an attractive target for antibiotics. It is the catalyst for the transfer of the
enolpyruvyl moiety of phosphoenol pyruvate (PEP) to the 3’ hydroxyl group of UDP-N-
acetylglucosamine (UNAG). Before the reaction proceeds the substrates must bind to
MurA in the strict order of UNAG before PEP. The next step is to protonate PEP,
resulting in an oxocarbenium ion which as a whole is added to the (N-acetylglucosamine)
sugar. A proton is then removed from the C-3 atom of the PEP moiety, leading to
separation of the inorganic phophate (Pi) from the adduct. The remaining product is
Enolpyruvyl-UDP-N-acetylglucosamine.
MurA is organized structurally as a two-domain protein with a deep cleft between
domains. It has an inside-out α/β barrell fold built up from sixfold repetition of one
folding unit. MurA shares this unusual fold with a protein of similar function but only
25% sequence identity, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). The
hinge of MurA is in the ranges 18-21 and 228-231 according to Schonbrunn et al.[84]
The results for this protein are shown in Figure 8. It is composed of a continuous domain
(residues 21-228, in green) and a discontinuous domain[112] (residues 1-20 and 229-419,
in pink and blue, respectively). There is a clear region of high FlexOracle energy and
another of intermediate energy, with the boundary arguably at residue 232. The N-
terminal boundary of the continuous domain is less clear.
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