 |
PDBsum entry 4trm
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Oxidoreductase
|
PDB id
|
|
|
|
4trm
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Oxidoreductase
|
|
|
Title:
|
|
Structure of the apo form of inha from mycobacterium tuberculosis
|
|
Structure:
|
|
Enoyl-[acyl-carrier-protein] reductase [nadh]. Chain: a, b, c, d, e, f. Synonym: nadh-dependent enoyl-acp reductase. Engineered: yes
|
|
Source:
|
|
Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: inha. Expressed in: escherichia coli. Expression_system_taxid: 511693.
|
|
Resolution:
|
|
|
1.80Å
|
R-factor:
|
0.190
|
R-free:
|
0.219
|
|
|
Authors:
|
|
A.Chollet,S.Julien,L.Mourey,L.Maveyraud
|
|
Key ref:
|
|
A.Chollet
et al.
(2015).
Crystal structure of the enoyl-ACP reductase of Mycobacterium tuberculosis (InhA) in the apo-form and in complex with the active metabolite of isoniazid pre-formed by a biomimetic approach.
J Struct Biol,
190,
328-337.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
17-Jun-14
|
Release date:
|
29-Apr-15
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P9WGR1
(INHA_MYCTU) -
Enoyl-[acyl-carrier-protein] reductase [NADH] from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
|
|
|
|
Seq:
Struc:
|
|
|
|
269 a.a.
256 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.1.3.1.9
- enoyl-[acyl-carrier-protein] reductase (NADH).
|
|
|
|
|
|
|
Reaction:
|
|
a 2,3-saturated acyl-[ACP] + NAD+ = a (2E)-enoyl-[ACP] + NADH + H+
|
|
|
|
|
|
2,3-saturated acyl-[ACP]
|
+
|
NAD(+)
|
=
|
(2E)-enoyl-[ACP]
|
+
|
NADH
|
+
|
H(+)
|
|
|
|
|
|
|
|
|
|
|
|
|
Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
DOI no:
|
J Struct Biol
190:328-337
(2015)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Crystal structure of the enoyl-ACP reductase of Mycobacterium tuberculosis (InhA) in the apo-form and in complex with the active metabolite of isoniazid pre-formed by a biomimetic approach.
|
|
A.Chollet,
L.Mourey,
C.Lherbet,
A.Delbot,
S.Julien,
M.Baltas,
J.Bernadou,
G.Pratviel,
L.Maveyraud,
V.Bernardes-Génisson.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
InhA is an enoyl-ACP reductase of Mycobacterium tuberculosis implicated in the
biosynthesis of mycolic acids, essential constituents of the mycobacterial cell
wall. To date, this enzyme is considered as a promising target for the discovery
of novel antitubercular drugs. In this work, we describe the first crystal
structure of the apo form of the wild-type InhA at 1.80Å resolution as well as
the crystal structure of InhA in complex with the synthetic metabolite of the
antitubercular drug isoniazid refined to 1.40Å. This metabolite, synthesized in
the absence of InhA, is able to displace and replace the cofactor NADH in the
enzyme active site. This work provides a unique opportunity to enlighten the
structural adaptation of apo-InhA to the binding of the NADH cofactor or of the
isoniazid adduct. In addition, a differential scanning fluorimetry study of
InhA, in the apo-form as well as in the presence of NAD(+), NADH and INH-NADH
was performed showing that binding of the INH-NADH adduct had a strong
stabilizing effect.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
