› 5ixs

X-ray diffraction
2.05Å resolution

Lactate Dehydrogenase in complex with hydroxylactam inhibitor compound 9: (6R)-3-[(2-chlorophenyl)sulfanyl]-4-hydroxy-6-(3-hydroxyphenyl)-6-(thiophen-3-yl)-5,6-dihydropyridin-2(1H)-one

Released:
DOI: 10.2210/pdb5ixs/pdb
PDB entry 5ixs coloured by chain, front view.
PDB entry 5ixs coloured by chain, side view.
PDB entry 5ixs coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Cell Active Hydroxylactam Inhibitors of Human Lactate Dehydrogenase with Oral Bioavailability in Mice.
Purkey HE, Robarge K, Chen J, Chen Z, Corson LB, Ding CZ, DiPasquale AG, Dragovich PS, Eigenbrot C, Evangelista M, Fauber BP, Gao Z, Ge H, Hitz A, Ho Q, Labadie SS, Lai KW, Liu W, Liu Y, Li C, Ma S, Malek S, O'Brien T, Pang J, Peterson D, Salphati L, Sideris S, Ultsch M, Wei B, Yen I, Yue Q, Zhang H, Zhou A
ACS Med Chem Lett 7 896-901 (2016)
PMID: 27774125

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: 331 amino acids
Theoretical weight: 36.6 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P00338 (Residues: 2-332; Coverage: 100%)
Gene names: LDHA, PIG19
Sequence domains:
Structure domains:

Ligands and Environments


Cofactor: Ligand TXD 3 x TXD

Cofactor: Ligand NAI 1 x NAI
3 bound ligands:
Ligand EPE 3 x EPE
Ligand 6EY 4 x 6EY
Ligand SO4 4 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL11-1
Spacegroup: P21
Unit cell:
a: 74.624Å b: 81.229Å c: 104.797Å
α: 90° β: 97.56° γ: 90°
R-values:
R R work R free
0.175 0.174 0.221
Expression system: Escherichia coli

Quick links

Citations

9 review citations

The Metabolic Landscape of Lung Cancer: New Insights in a Disturbed Glucose Metabolism.
Vanhove et al. (2019)
8 more

3 mentions without citation

Three-Dimensional Analysis of the Interactions between hLDH5 and Its Inhibitors.
Poli et al. (2017)
2 more