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PDBsum entry 4zqn
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Oxidoreductase/oxidoreductase inhibitor
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PDB id
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4zqn
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PDB id:
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| Name: |
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Oxidoreductase/oxidoreductase inhibitor
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Title:
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Crystal structure of the catalytic domain of the inosine monophosphate dehydrogenase from mycobacterium tuberculosis in the complex with imp and the inhibitor p41
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Structure:
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Inosine-5'-monophosphate dehydrogenase,inosine-5'- monophosphate dehydrogenase. Chain: a. Fragment: unp residues 1-125 and 253-529 linked by linker (gly gly). Synonym: impdh. Engineered: yes
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Source:
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Mycobacterium tuberculosis (strain atcc 25618 / h37rv). Organism_taxid: 83332. Strain: atcc 25618 / h37rv. Gene: guab, guab2, rv3411c, mtcy78.17. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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2.00Å
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R-factor:
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0.180
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R-free:
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0.221
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Authors:
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Y.Kim,M.Makowska-Grzyska,M.Gu,M.Kavitha,L.Hedstrom,W.F.Anderson, A.Joachimiak,Center For Structural Genomics Of Infectious Diseases (Csgid)
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Key ref:
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M.Makowska-Grzyska
et al.
(2015).
Mycobacterium tuberculosis IMPDH in Complexes with Substrates, Products and Antitubercular Compounds.
Plos One,
10,
e0138976.
PubMed id:
DOI:
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Date:
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10-May-15
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Release date:
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17-Jun-15
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PROCHECK
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Headers
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References
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P9WKI7
(IMDH_MYCTU) -
Inosine-5'-monophosphate dehydrogenase from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
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Seq:
Struc:
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529 a.a.
353 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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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Enzyme class:
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E.C.1.1.1.205
- Imp dehydrogenase.
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Pathway:
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AMP and GMP Biosynthesis
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Reaction:
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IMP + NAD+ + H2O = XMP + NADH + H+
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IMP
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+
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NAD(+)
Bound ligand (Het Group name = )
corresponds exactly
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+
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H2O
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=
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XMP
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+
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NADH
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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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DOI no:
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Plos One
10:e0138976
(2015)
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PubMed id:
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Mycobacterium tuberculosis IMPDH in Complexes with Substrates, Products and Antitubercular Compounds.
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M.Makowska-Grzyska,
Y.Kim,
S.K.Gorla,
Y.Wei,
K.Mandapati,
M.Zhang,
N.Maltseva,
G.Modi,
H.I.Boshoff,
M.Gu,
C.Aldrich,
G.D.Cuny,
L.Hedstrom,
A.Joachimiak.
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ABSTRACT
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Tuberculosis (TB) remains a worldwide problem and the need for new drugs is
increasingly more urgent with the emergence of multidrug- and extensively-drug
resistant TB. Inosine 5'-monophosphate dehydrogenase 2 (IMPDH2) from
Mycobacterium tuberculosis (Mtb) is an attractive drug target. The enzyme
catalyzes the conversion of inosine 5'-monophosphate into xanthosine
5'-monophosphate with the concomitant reduction of NAD+ to NADH. This reaction
controls flux into the guanine nucleotide pool. We report seventeen selective
IMPDH inhibitors with antitubercular activity. The crystal structures of a
deletion mutant of MtbIMPDH2 in the apo form and in complex with the product XMP
and substrate NAD+ are determined. We also report the structures of complexes
with IMP and three structurally distinct inhibitors, including two with
antitubercular activity. These structures will greatly facilitate the
development of MtbIMPDH2-targeted antibiotics.
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