Structural highlights
4c5c is a 2 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , |
| Related: | 4c5a, 4c5b |
| Activity: | D-alanine--D-alanine ligase, with EC number 6.3.2.4 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[C4ZRI7_ECOBW] Cell wall formation.[HAMAP-Rule:MF_00047][SAAS:SAAS00058712]
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.
References
- ↑ 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
