The X-ray crystal structures of D-alanyl-D-alanine ligase in complex ADP and D-cycloserine phosphateThe X-ray crystal structures of D-alanyl-D-alanine ligase in complex ADP and D-cycloserine phosphate

Structural highlights

4c5a is a 3 chain structure with sequence from Escherichia coli K-12 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.65Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DDLB_ECOLI Cell wall formation.

Publication Abstract from PubMed

D-cycloserine is an antibiotic which targets sequential bacterial cell wall peptidoglycan biosynthesis enzymes: alanine racemase and D-alanine:D-alanine ligase. By a combination of structural, chemical and mechanistic studies here we show that the inhibition of D-alanine:D-alanine ligase by the antibiotic D-cycloserine proceeds via a distinct phosphorylated form of the drug. This mechanistic insight reveals a bimodal mechanism of action for a single antibiotic on different enzyme targets and has significance for the design of future inhibitor molecules based on this chemical structure.

Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine.,Batson S, de Chiara C, Majce V, Lloyd AJ, Gobec S, Rea D, Fulop V, Thoroughgood CW, Simmons KJ, Dowson CG, Fishwick CWG, de Carvalho LPS, Roper DI Nat Commun. 2017 Dec 5;8(1):1939. doi: 10.1038/s41467-017-02118-7. PMID:29208891[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Batson S, de Chiara C, Majce V, Lloyd AJ, Gobec S, Rea D, Fulop V, Thoroughgood CW, Simmons KJ, Dowson CG, Fishwick CWG, de Carvalho LPS, Roper DI. Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine. Nat Commun. 2017 Dec 5;8(1):1939. doi: 10.1038/s41467-017-02118-7. PMID:29208891 doi:http://dx.doi.org/10.1038/s41467-017-02118-7

4c5a, resolution 1.65Å

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