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Title
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Determination of the MurD mechanism through crystallographic analysis of enzyme complexes.
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Authors
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J.A.Bertrand,
G.Auger,
L.Martin,
E.Fanchon,
D.Blanot,
D.Le Beller,
J.van Heijenoort,
O.Dideberg.
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Ref.
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J Mol Biol, 1999,
289,
579-590.
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PubMed id
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Abstract
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UDP -N- acetylmuramoyl- L -alanine: D -glutamate (MurD) ligase catalyses the
addition of d -glutamate to the nucleotide precursor UDP -N- acetylmuramoyl- L
-alanine (UMA). The crystal structures of three complexes of Escherichia coli
MurD with a variety of substrates and products have been determined to high
resolution. These include (1) the quaternary complex of MurD, the substrate UMA,
the product ADP, and Mg2+, (2) the quaternary complex of MurD, the substrate
UMA, the product ADP, and Mn2+, and (3) the binary complex of MurD with the
product UDP - N- acetylmuramoyl- L -alanine- D -glutamate (UMAG). The reaction
mechanism supported by these structures proceeds by the phosphorylation of the
C-terminal carboxylate group of UMA by the gamma-phosphate group of ATP to form
an acyl-phosphate intermediate, followed by the nucleophilic attack by the amino
group of D-glutamate to produce UMAG. A key feature in the reaction intermediate
is the presence of two magnesium ions bridging negatively charged groups.
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