4C5B

The X-ray crystal structure of D-alanyl-D-alanine ligase in complex with ATP and D-ala-D-ala

Summary for 4C5B

• Entry DOI: 10.2210/pdb4c5b/pdb
• Related: 4C5A 4C5C
• Descriptor: D-ALANINE--D-ALANINE LIGASE, ADENOSINE-5'-DIPHOSPHATE, D-ALANINE, ... (8 entities in total)
• Functional Keywords: ligase, ddlb
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 2
• Total formula weight: 73411.47

Authors

Batson, S.,Majce, V.,Lloyd, A.J.,Rea, D.,Fishwick, C.W.G.,Simmons, K.J.,Fulop, V.,Roper, D.I. (deposition date: 2013-09-10, release date: 2015-01-21, Last modification date: 2023-12-20)

Primary citation

Batson, S.,de Chiara, C.,Majce, V.,Lloyd, A.J.,Gobec, S.,Rea, D.,Fulop, V.,Thoroughgood, C.W.,Simmons, K.J.,Dowson, C.G.,Fishwick, C.W.G.,de Carvalho, L.P.S.,Roper, D.I.
Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine.
Nat Commun, 8:1939-1939, 2017

PubMed Abstract: 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.

PubMed: 29208891
DOI: 10.1038/s41467-017-02118-7

Experimental method

X-RAY DIFFRACTION (1.5 Å)