› 6ng4

X-ray diffraction
1.78Å resolution

Structure of human neuronal nitric oxide synthase R354A/G357D mutant heme domain in complex with (R)-6-(3-fluoro-5-(2-(pyrrolidin-2-yl)ethyl)phenethyl)-4-methylpyridin-2-amine

Released:
DOI: 10.2210/pdb6ng4/pdb
PDB entry 6ng4 coloured by chain, front view.
PDB entry 6ng4 coloured by chain, side view.
PDB entry 6ng4 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Optimization of Blood-Brain Barrier Permeability with Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibitors Having a 2-Aminopyridine Scaffold.
Do HT, Li H, Chreifi G, Poulos TL, Silverman RB
J Med Chem 62 2690-2707 (2019)
PMID: 30802056

Function and Biology Details

Reaction catalysed: 
(1a) 2 L-arginine + 2 NADPH + 2 O(2) = 2 N(omega)-hydroxy-L-arginine + 2 NADP(+) + 2 H(2)O
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-151514 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Nitric oxide synthase 1 Chains: A, B
Molecule details ›
Chains: A, B
Length: 421 amino acids
Theoretical weight: 48.78 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P29475 (Residues: 302-722; Coverage: 29%)
Gene name: NOS1
Sequence domains: Nitric oxide synthase, oxygenase domain
Structure domains:

Ligands and Environments


Cofactor: Ligand HEM 2 x HEM
4 bound ligands:
Ligand H4B 2 x H4B
Ligand ZN 1 x ZN
Ligand KMA 2 x KMA
Ligand GOL 3 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL12-2
Spacegroup: P212121
Unit cell:
a: 52.393Å b: 121.629Å c: 164.007Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.18 0.178 0.215
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

8 citation in other articles

2-Aminopyridines with a shortened amino sidechain as potent, selective, and highly permeable human neuronal nitric oxide synthase inhibitors.
Vasu et al. (2022)
7 more