 |
PDBsum entry 4c5c
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Inhibition of d-Ala:d-Ala ligase through a phosphorylated form of the antibiotic d-Cycloserine.
|
|
|
Authors
|
|
S.Batson,
C.De chiara,
V.Majce,
A.J.Lloyd,
S.Gobec,
D.Rea,
V.Fülöp,
C.W.Thoroughgood,
K.J.Simmons,
C.G.Dowson,
C.W.G.Fishwick,
L.P.S.De carvalho,
D.I.Roper.
|
|
|
Ref.
|
|
Nat Commun, 2017,
8,
1939.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
