› 4zvv

X-ray diffraction
2.2Å resolution

Lactate dehydrogenase A in complex with a trisubstituted piperidine-2,4-dione inhibitor GNE-140

Released:
DOI: 10.2210/pdb4zvv/pdb
PDB entry 4zvv coloured by chain, front view.
PDB entry 4zvv coloured by chain, side view.
PDB entry 4zvv coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Metabolic plasticity underpins innate and acquired resistance to LDHA inhibition.
Boudreau A, Purkey HE, Hitz A, Robarge K, Peterson D, Labadie S, Kwong M, Hong R, Gao M, Del Nagro C, Pusapati R, Ma S, Salphati L, Pang J, Zhou A, Lai T, Li Y, Chen Z, Wei B, Yen I, Sideris S, McCleland M, Firestein R, Corson L, Vanderbilt A, Williams S, Daemen A, Belvin M, Eigenbrot C, Jackson PK, Malek S, Hatzivassiliou G, Sampath D, Evangelista M, O'Brien T
Nat Chem Biol 12 779-86 (2016)
PMID: 27479743

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-132412 (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: 332 amino acids
Theoretical weight: 36.73 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P00338 (Residues: 1-332; Coverage: 100%)
Gene names: LDHA, PIG19
Sequence domains:
Structure domains:

Ligands and Environments


Cofactor: Ligand NAD 4 x NAD
2 bound ligands:
Ligand SO4 7 x SO4
Ligand GN0 4 x GN0
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL17U
Spacegroup: P21
Unit cell:
a: 79.164Å b: 81.288Å c: 102.47Å
α: 90° β: 98.31° γ: 90°
R-values:
R R work R free
0.233 0.232 0.259
Expression system: Escherichia coli

Quick links

Citations

39 review citations

Understanding the Intersections between Metabolism and Cancer Biology.
Vander Heiden et al. (2017)
38 more

8 mentions without citation

Small Molecule-Based Enzyme Inhibitors in the Treatment of Primary Hyperoxalurias.
Moya-Garzon et al. (2021)
7 more