› 5kgs

X-ray diffraction
2.1Å resolution

Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with an inhibitor optimized from HTS lead: 5-[4-(1,3-benzodioxol-5-ylcarbonyl)piperazin-1-yl]-2,3-dihydroinden-1-one

Released:
DOI: 10.2210/pdb5kgs/pdb
PDB entry 5kgs coloured by chain, front view.
PDB entry 5kgs coloured by chain, side view.
PDB entry 5kgs coloured by chain, top view.
Source organism: Mycobacterium tuberculosis variant bovis AF2122/97
Primary publication:
Structure-Based Optimization of Pyridoxal 5'-Phosphate-Dependent Transaminase Enzyme (BioA) Inhibitors that Target Biotin Biosynthesis in Mycobacterium tuberculosis.
Liu F, Dawadi S, Maize KM, Dai R, Park SW, Schnappinger D, Finzel BC, Aldrich CC
J Med Chem 60 5507-5520 (2017)
PMID: 28594172

Function and Biology Details

Reaction catalysed: 
S-adenosyl-L-methionine + 8-amino-7-oxononanoate = S-adenosyl-4-methylthio-2-oxobutanoate + 7,8-diaminononanoate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-141268 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Adenosylmethionine-8-amino-7-oxononanoate aminotransferase Chains: A, B
Molecule details ›
Chains: A, B
Length: 457 amino acids
Theoretical weight: 48.54 KDa
Source organism: Mycobacterium tuberculosis variant bovis AF2122/97
Expression system: Escherichia coli
UniProt:
  • Canonical: P0A4X7 (Residues: 1-437; Coverage: 100%)
Gene names: BQ2027_MB1595, bioA
Sequence domains: Aminotransferase class-III
Structure domains:

Ligands and Environments


Cofactor: Ligand PLP 2 x PLP
2 bound ligands:
Ligand 6SR 2 x 6SR
Ligand PGE 2 x PGE
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P212121
Unit cell:
a: 63.186Å b: 65.948Å c: 203.898Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.177 0.175 0.219
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Hit Generation in TB Drug Discovery: From Genome to Granuloma.
Yuan et al. (2018)
2 more

2 mentions without citation

Structure-Based Optimization of Pyridoxal 5'-Phosphate-Dependent Transaminase Enzyme (BioA) Inhibitors that Target Biotin Biosynthesis in Mycobacterium tuberculosis.
Liu et al. (2017)
1 more