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PDBsum entry 4pqa
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Hydrolase/hydrolase inhibitor
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PDB id
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4pqa
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PDB id:
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| Name: |
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Hydrolase/hydrolase inhibitor
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Title:
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Crystal structure of succinyl-diaminopimelate desuccinylase from neisseria meningitidis mc58 in complex with the inhibitor captopril
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Structure:
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Succinyl-diaminopimelate desuccinylase. Chain: a. Synonym: sdap desuccinylase, n-succinyl-ll-2,6-diaminoheptanedioate amidohydrolase. Engineered: yes
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Source:
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Neisseria meningitidis. Organism_taxid: 122586. Strain: mc58. Gene: dape, nmb1530. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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1.78Å
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R-factor:
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0.164
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R-free:
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0.196
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Authors:
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B.Nocek,A.Starus,R.Holz,W.F.Anderson,A.Joachimiak,Center For Structural Genomics Of Infectious Diseases (Csgid)
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Key ref:
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A.Starus
et al.
(2015).
Inhibition of the dapE-Encoded N-Succinyl-L,L-diaminopimelic Acid Desuccinylase from Neisseria meningitidis by L-Captopril.
Biochemistry,
54,
4834-4844.
PubMed id:
DOI:
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Date:
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01-Mar-14
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Release date:
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30-Apr-14
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PROCHECK
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Headers
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References
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Q9JYL2
(DAPE_NEIMB) -
Succinyl-diaminopimelate desuccinylase from Neisseria meningitidis serogroup B (strain MC58)
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Seq:
Struc:
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381 a.a.
375 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.3.5.1.18
- succinyl-diaminopimelate desuccinylase.
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Pathway:
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Lysine biosynthesis (later stages)
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Reaction:
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N-succinyl-(2S,6S)-2,6-diaminopimelate + H2O = (2S,6S)-2,6- diaminopimelate + succinate
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N-succinyl-(2S,6S)-2,6-diaminopimelate
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+
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H2O
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=
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(2S,6S)-2,6- diaminopimelate
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+
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succinate
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Biochemistry
54:4834-4844
(2015)
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PubMed id:
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Inhibition of the dapE-Encoded N-Succinyl-L,L-diaminopimelic Acid Desuccinylase from Neisseria meningitidis by L-Captopril.
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A.Starus,
B.Nocek,
B.Bennett,
J.A.Larrabee,
D.L.Shaw,
W.Sae-Lee,
M.T.Russo,
D.M.Gillner,
M.Makowska-Grzyska,
A.Joachimiak,
R.C.Holz.
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ABSTRACT
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Binding of the competitive inhibitor L-captopril to the dapE-encoded
N-succinyl-L,L-diaminopimelic acid desuccinylase from Neisseria meningitidis
(NmDapE) was examined by kinetic, spectroscopic, and crystallographic methods.
L-Captopril, an angiotensin-converting enzyme (ACE) inhibitor, was previously
shown to be a potent inhibitor of the DapE from Haemophilus influenzae (HiDapE)
with an IC50 of 3.3 μM and a measured Ki of 1.8 μM and displayed a
dose-responsive antibiotic activity toward Escherichia coli. L-Captopril is also
a competitive inhibitor of NmDapE with a Ki of 2.8 μM. To examine the nature of
the interaction of L-captopril with the dinuclear active site of DapE, we have
obtained electron paramagnetic resonance (EPR) and magnetic circular dichroism
(MCD) data for the enzymatically hyperactive Co(II)-substituted forms of both
HiDapE and NmDapE. EPR and MCD data indicate that the two Co(II) ions in DapE
are antiferromagnetically coupled, yielding an S = 0 ground state, and suggest a
thiolate bridge between the two metal ions. Verification of a thiolate-bridged
dinuclear complex was obtained by determining the three-dimensional X-ray
crystal structure of NmDapE in complex with L-captopril at 1.8 Å resolution.
Combination of these data provides new insights into binding of L-captopril to
the active site of DapE enzymes as well as important inhibitor-active site
residue interaction's. Such information is critical for the design of new,
potent inhibitors of DapE enzymes.
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