› 4q6r

X-ray diffraction
2.4Å resolution

Crystal structure of human sphingosine-1-phosphate lyase in complex with inhibitor 6-[(2R)-4-(4-benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile

Released:
DOI: 10.2210/pdb4q6r/pdb
PDB entry 4q6r coloured by chain, front view.
PDB entry 4q6r coloured by chain, side view.
PDB entry 4q6r coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Orally active 7-substituted (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitriles as active-site inhibitors of sphingosine 1-phosphate lyase for the treatment of multiple sclerosis.
Weiler S, Braendlin N, Beerli C, Bergsdorf C, Schubart A, Srinivas H, Oberhauser B, Billich A
J Med Chem 57 5074-84 (2014)
PMID: 24809814

Function and Biology Details

Reaction catalysed: 
Sphinganine 1-phosphate = phosphoethanolamine + palmitaldehyde
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-131939 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Sphingosine-1-phosphate lyase 1 Chains: A, B
Molecule details ›
Chains: A, B
Length: 511 amino acids
Theoretical weight: 56.87 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O95470 (Residues: 62-568; Coverage: 89%)
Gene names: KIAA1252, SGPL1
Sequence domains: Pyridoxal-dependent decarboxylase conserved domain
Structure domains:

Ligands and Environments

4 bound ligands:
Ligand SIN 1 x SIN
Ligand GOL 1 x GOL
Ligand 30J 2 x 30J
Ligand PO4 1 x PO4
1 modified residue:
Ligand LLP 2 x LLP

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P21212
Unit cell:
a: 127.985Å b: 130.532Å c: 68.224Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.216 0.178 0.206
Expression system: Spodoptera frugiperda

Quick links

Citations

10 review citations

Targeting sphingosine-1-phosphate signaling in lung diseases.
Ebenezer et al. (2016)
9 more

13 mentions without citation

Sphingolipid biosynthesis in man and microbes.
Harrison et al. (2018)
12 more