› 5ixy

X-ray diffraction
3Å resolution

Lactate Dehydrogenase in complex with hydroxylactam inhibitor compound 31: (2~{S})-5-(2-chlorophenyl)sulfanyl-2-(4-morpholin-4-ylphenyl)-4-oxidanyl-2-thiophen-3-yl-1,3-dihydropyridin-6-one

Released:
DOI: 10.2210/pdb5ixy/pdb
PDB entry 5ixy coloured by chain, front view.
PDB entry 5ixy coloured by chain, side view.
PDB entry 5ixy 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 NAD 4 x NAD
2 bound ligands:
Ligand SO4 7 x SO4
Ligand GN2 4 x GN2
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL17U
Spacegroup: P21
Unit cell:
a: 78.452Å b: 80.696Å c: 102.236Å
α: 90° β: 97.9° γ: 90°
R-values:
R R work R free
0.237 0.236 0.279
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