› 4ajj

X-ray diffraction
1.75Å resolution

rat LDHA in complex with 2-((3,4-dimethoxyphenyl)methyl))propanedioic acid and N-(2-methyl-1,3-benzothiazol-6-yl)-3-ureido-propanamide

Released:
DOI: 10.2210/pdb4ajj/pdb
PDB entry 4ajj coloured by chain, front view.
PDB entry 4ajj coloured by chain, side view.
PDB entry 4ajj coloured by chain, top view.
Source organism: Rattus norvegicus
Primary publication:
Design and synthesis of novel lactate dehydrogenase A inhibitors by fragment-based lead generation.
Ward RA, Brassington C, Breeze AL, Caputo A, Critchlow S, Davies G, Goodwin L, Hassall G, Greenwood R, Holdgate GA, Mrosek M, Norman RA, Pearson S, Tart J, Tucker JA, Vogtherr M, Whittaker D, Wingfield J, Winter J, Hudson K
J Med Chem 55 3285-306 (2012)
PMID: 22417091

Function and Biology Details

Reaction catalysed: 
(S)-lactate + NAD(+) = pyruvate + NADH
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-138140 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
L-lactate dehydrogenase A chain Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 331 amino acids
Theoretical weight: 36.36 KDa
Source organism: Rattus norvegicus
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P04642 (Residues: 2-332; Coverage: 100%)
Gene names: Ldh-1, Ldh1, Ldha
Sequence domains:
Structure domains:

Ligands and Environments

5 bound ligands:
Ligand 88S 4 x 88S
Ligand MLI 2 x MLI
Ligand 88R 2 x 88R
Ligand DMS 1 x DMS
Ligand GOL 1 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E
Spacegroup: P21
Unit cell:
a: 62.141Å b: 81.892Å c: 128.986Å
α: 90° β: 96.06° γ: 90°
R-values:
R R work R free
0.146 0.144 0.173
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

19 review citations

Twenty years on: the impact of fragments on drug discovery.
Erlanson et al. (2016)
18 more

1 mention without citation

Survey of phosphorylation near drug binding sites in the Protein Data Bank (PDB) and their effects.
Smith et al. (2015)