 |
PDBsum entry 4b6c
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Isomerase
|
|
|
Title:
|
|
Structure of the m. Smegmatis gyrb atpase domain in complex with an aminopyrazinamide
|
|
Structure:
|
|
DNA gyrase subunit b,DNA gyrase subunit b,DNA gyrase subunit b. Chain: a, b. Fragment: atpase domain, residues 9-102,123-213,246-255,atpase domain, residues 9-102,123-213,246-255,atpase domain, residues 9-102, 123-213,246-255. Engineered: yes. Mutation: yes
|
|
Source:
|
|
Mycobacterium smegmatis. Organism_taxid: 1772. Gene: gyrb. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008
|
|
Resolution:
|
|
|
2.20Å
|
R-factor:
|
0.202
|
R-free:
|
0.254
|
|
|
Authors:
|
|
J.A.Tucker,P.S.Shirude,P.Madhavapeddi,S.Hussein,R.Basu,S.Ghorpade
|
|
Key ref:
|
|
P.S.Shirude
et al.
(2013).
Aminopyrazinamides: novel and specific GyrB inhibitors that kill replicating and nonreplicating Mycobacterium tuberculosis.
Acs Chem Biol,
8,
519-523.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
09-Aug-12
|
Release date:
|
23-Jan-13
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P0C559
(GYRB_MYCSM) -
DNA gyrase subunit B from Mycolicibacterium smegmatis
|
|
|
|
Seq:
Struc:
|
|
|
|
675 a.a.
161 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
*
PDB and UniProt seqs differ
at 10 residue positions (black
crosses)
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.5.6.2.2
- Dna topoisomerase (ATP-hydrolyzing).
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Acs Chem Biol
8:519-523
(2013)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Aminopyrazinamides: novel and specific GyrB inhibitors that kill replicating and nonreplicating Mycobacterium tuberculosis.
|
|
P.S.Shirude,
P.Madhavapeddi,
J.A.Tucker,
K.Murugan,
V.Patil,
H.Basavarajappa,
A.V.Raichurkar,
V.Humnabadkar,
S.Hussein,
S.Sharma,
V.K.Ramya,
C.B.Narayan,
T.S.Balganesh,
V.K.Sambandamurthy.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Aminopyrazinamides originated from a high throughput screen targeting the
Mycobacterium smegmatis (Msm) GyrB ATPase. This series displays chemical
tractability, robust structure-activity relationship, and potent antitubercular
activity. The crystal structure of Msm GyrB in complex with one of the
aminopyrazinamides revealed promising attributes of specificity against other
broad spectrum pathogens and selectivity against eukaryotic kinases due to novel
interactions at hydrophobic pocket, unlike other known GyrB inhibitors. The
aminopyrazinamides display excellent mycobacterial kill under in vitro,
intracellular, and hypoxic conditions.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
