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PDBsum entry 6sql
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Oxidoreductase
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PDB id
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6sql
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PDB id:
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| Name: |
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Oxidoreductase
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Title:
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Crystal structure of m. Tuberculosis inha in complex with NAD+ and n- (3-(aminomethyl)phenyl)-5-chloro-3-methylbenzo[b]thiophene-2- sulfonamide
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Structure:
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Enoyl-[acyl-carrier-protein] reductase [nadh]. Chain: a. Synonym: enoyl-acp reductase,fas-ii enoyl-acp reductase,nadh- dependent 2-trans-enoyl-acp reductase. Engineered: yes
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Source:
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Mycobacterium tuberculosis h37rv. Organism_taxid: 83332. Gene: inha, rv1484, mtcy277.05. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008
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Resolution:
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2.35Å
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R-factor:
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0.164
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R-free:
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0.204
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Authors:
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V.Mendes,M.Sabbah,A.G.Coyne,C.Abell,T.L.Blundell
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Key ref:
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M.Sabbah
et al.
(2020).
Fragment-Based Design of Mycobacterium tuberculosis InhA Inhibitors.
J Med Chem,
63,
4749-4761.
PubMed id:
DOI:
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Date:
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04-Sep-19
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Release date:
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22-Apr-20
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PROCHECK
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Headers
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References
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P9WGR1
(INHA_MYCTU) -
Enoyl-[acyl-carrier-protein] reductase [NADH] from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
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Seq:
Struc:
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269 a.a.
267 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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Enzyme class:
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E.C.1.3.1.9
- enoyl-[acyl-carrier-protein] reductase (NADH).
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Reaction:
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a 2,3-saturated acyl-[ACP] + NAD+ = a (2E)-enoyl-[ACP] + NADH + H+
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2,3-saturated acyl-[ACP]
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+
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NAD(+)
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=
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(2E)-enoyl-[ACP]
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+
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NADH
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+
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H(+)
Bound ligand (Het Group name = )
matches with 83.33% similarity
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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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J Med Chem
63:4749-4761
(2020)
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PubMed id:
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Fragment-Based Design of Mycobacterium tuberculosis InhA Inhibitors.
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M.Sabbah,
V.Mendes,
R.G.Vistal,
D.M.G.Dias,
M.Záhorszká,
K.MikuĊĦová,
J.Korduláková,
A.G.Coyne,
T.L.Blundell,
C.Abell.
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ABSTRACT
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Tuberculosis (TB) remains a leading cause of mortality among infectious diseases
worldwide. InhA has been the focus of numerous drug discovery efforts as this is
the target of the first line pro-drug isoniazid. However, with resistance to
this drug becoming more common, the aim has been to find new clinical candidates
that directly inhibit this enzyme and that do not require activation by the
catalase peroxidase KatG, thus circumventing the majority of the resistance
mechanisms. In this work, the screening and validation of a fragment library are
described, and the development of the fragment hits using a fragment growing
strategy was employed, which led to the development of InhA inhibitors with
affinities of up to 250 nM.
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Links
