› 4bae

X-ray diffraction
2.35Å resolution

Optimisation of pyrroleamides as mycobacterial GyrB ATPase inhibitors: Structure Activity Relationship and in vivo efficacy in the mouse model of tuberculosis

Released:
DOI: 10.2210/pdb4bae/pdb
PDB entry 4bae coloured by chain, front view.
PDB entry 4bae coloured by chain, side view.
PDB entry 4bae coloured by chain, top view.
Source organism: Mycolicibacterium smegmatis
Primary publication:
Optimization of pyrrolamides as mycobacterial GyrB ATPase inhibitors: structure-activity relationship and in vivo efficacy in a mouse model of tuberculosis.
P SH, Solapure S, Mukherjee K, Nandi V, Waterson D, Shandil R, Balganesh M, Sambandamurthy VK, Raichurkar AK, Deshpande A, Ghosh A, Awasthy D, Shanbhag G, Sheikh G, McMiken H, Puttur J, Reddy J, Werngren J, Read J, Kumar M, R M, Chinnapattu M, Madhavapeddi P, Manjrekar P, Basu R, Gaonkar S, Sharma S, Hoffner S, Humnabadkar V, Subbulakshmi V, Panduga V
Antimicrob Agents Chemother 58 61-70 (2014)
PMID: 24126580

Function and Biology Details

Reaction catalysed: 
ATP-dependent breakage, passage and rejoining of double-stranded DNA
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-143020 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
DNA gyrase subunit B Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 205 amino acids
Theoretical weight: 22.78 KDa
Source organism: Mycolicibacterium smegmatis
Expression system: Escherichia coli
UniProt:
  • Canonical: P0C559 (Residues: 19-255; Coverage: 30%)
Gene name: gyrB
Sequence domains: Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
Structure domains: Histidine kinase-like ATPase, C-terminal domain

Ligands and Environments

3 bound ligands:
Ligand CA 4 x CA
Ligand RWX 4 x RWX
Ligand SO4 4 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID23-1
Spacegroup: P21
Unit cell:
a: 59.191Å b: 78.249Å c: 89.75Å
α: 90° β: 90.01° γ: 90°
R-values:
R R work R free
0.196 0.194 0.237
Expression system: Escherichia coli

Quick links

Citations

5 review citations

DNA topoisomerase I and DNA gyrase as targets for TB therapy.
Nagaraja et al. (2017)
4 more

3 mentions without citation

Drug Discovery for Mycobacterium tuberculosis Using Structure-Based Computer-Aided Drug Design Approach.
Ejalonibu et al. (2021)
2 more