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PDBsum entry 4c5c
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PDB id:
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Ligase
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Title:
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The x-ray crystal structure of d-alanyl-d-alanine ligase in complex with adp and d-ala-d-ala
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Structure:
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D-alanine--d-alanine ligase. Chain: a, b. Synonym: d-ala-d-ala ligase, d-alanylalanine synthetase, d-alanyl-d- alanine ligase. Engineered: yes
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Source:
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Escherichia coli. Organism_taxid: 83333. Strain: k-12. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta.
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Resolution:
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1.40Å
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R-factor:
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0.181
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R-free:
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0.203
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Authors:
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S.Batson,V.Majce,A.J.Lloyd,D.Rea,C.W.G.Fishwick,K.J.Simmons,V.Fulop, D.I.Roper
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Key ref:
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S.Batson
et al.
(2017).
Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine.
Nat Commun,
8,
1939.
PubMed id:
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Date:
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10-Sep-13
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Release date:
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21-Jan-15
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PROCHECK
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Headers
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References
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P07862
(DDLB_ECOLI) -
D-alanine--D-alanine ligase B from Escherichia coli (strain K12)
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Seq:
Struc:
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306 a.a.
306 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.6.3.2.4
- D-alanine--D-alanine ligase.
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Pathway:
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Peptidoglycan Biosynthesis (Part 1)
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Reaction:
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2 D-alanine + ATP = D-alanyl-D-alanine + ADP + phosphate + H+
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2
×
D-alanine
Bound ligand (Het Group name = )
corresponds exactly
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+
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ATP
Bound ligand (Het Group name = )
corresponds exactly
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=
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D-alanyl-D-alanine
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+
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ADP
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+
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phosphate
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Nat Commun
8:1939
(2017)
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PubMed id:
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Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine.
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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.
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ABSTRACT
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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.
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