Crystal Structure of UDP-N-acetylmuramoyl-l-alanyl-d-glutamate:meso-Diaminopimelate Ligase from Escherichia Coli

UDP-N-acetylmuramoyl-l-alanyl-d-glutamate:meso-diaminopimelate ligase is a cytoplasmic enzyme that catalyzes the addition of meso-diaminopimelic acid to nucleotide precursor UDP-N-acetylmuramoyl-l-alanyl-d-glutamate in the biosynthesis of bacterial cell-wall peptidoglycan. The crystal structure of t...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-04, Vol.276 (14), p.10999-11006
Main Authors: Gordon, Elspeth, Flouret, Bernard, Chantalat, Laurent, van Heijenoort, Jean, Mengin-Lecreulx, Dominique, Dideberg, Otto
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Crystallization
Escherichia coli
Escherichia coli - chemistry
Escherichia coli - enzymology
Molecular Sequence Data
MurD protein
Peptide Synthases - chemistry
Peptidoglycan - chemistry
Peptidoglycan - metabolism
peptidoglycans
Protein Conformation
Sequence Alignment
UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-meso- diaminopimelate ligase
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Summary:UDP-N-acetylmuramoyl-l-alanyl-d-glutamate:meso-diaminopimelate ligase is a cytoplasmic enzyme that catalyzes the addition of meso-diaminopimelic acid to nucleotide precursor UDP-N-acetylmuramoyl-l-alanyl-d-glutamate in the biosynthesis of bacterial cell-wall peptidoglycan. The crystal structure of the Escherichia coli enzyme in the presence of the final product of the enzymatic reaction, UDP-MurNAc-l-Ala-γ-d-Glu-meso-A2pm, has been solved to 2.0 Å resolution. Phase information was obtained by multiwavelength anomalous dispersion using the K shell edge of selenium. The protein consists of three domains, two of which have a topology reminiscent of the equivalent domain found in the already established three-dimensional structure of the UDP-N-acetylmuramoyl-l-alanine: D-glutamate-ligase (MurD) ligase, which catalyzes the immediate previous step of incorporation of d-glutamic acid in the biosynthesis of the peptidoglycan precursor. The refined model reveals the binding site for UDP-MurNAc-l-Ala-γ-d-Glu-meso-A2pm, and comparison with the six known MurD structures allowed the identification of residues involved in the enzymatic mechanism. Interestingly, during refinement, an excess of electron density was observed, leading to the conclusion that, as in MurD, a carbamylated lysine residue is present in the active site. In addition, the structural determinant responsible for the selection of the amino acid to be added to the nucleotide precursor was identified.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M009835200