› 3r4m

X-ray diffraction
1.7Å resolution

Optimization of Potent, Selective, and Orally Bioavailable Pyrrolodinopyrimidine-containing Inhibitors of Heat Shock Protein 90. Identification of Development Candidate 2-amino-4-{4-chloro-2-[2-(4-fluoro-1H-pyrazol-1-yl)ethoxy]-6-methylphenyl}-N-(2,2-difluoropropyl)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxamide

Released:
DOI: 10.2210/pdb3r4m/pdb
PDB entry 3r4m coloured by chain, front view.
PDB entry 3r4m coloured by chain, side view.
PDB entry 3r4m coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Optimization of potent, selective, and orally bioavailable pyrrolodinopyrimidine-containing inhibitors of heat shock protein 90. Identification of development candidate 2-amino-4-{4-chloro-2-[2-(4-fluoro-1H-pyrazol-1-yl)ethoxy]-6-methylphenyl}-N-(2,2-difluoropropyl)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxamide.
Zehnder L, Bennett M, Meng J, Huang B, Ninkovic S, Wang F, Braganza J, Tatlock J, Jewell T, Zhou JZ, Burke B, Wang J, Maegley K, Mehta PP, Yin MJ, Gajiwala KS, Hickey MJ, Yamazaki S, Smith E, Kang P, Sistla A, Dovalsantos E, Gehring MR, Kania R, Wythes M, Kung PP
J Med Chem 54 3368-85 (2011)
PMID: 21438541

Function and Biology Details

Reaction catalysed: 
ATP + H(2)O = ADP + phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-139817 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Heat shock protein HSP 90-alpha Chain: A
Molecule details ›
Chain: A
Length: 228 amino acids
Theoretical weight: 25.66 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P07900 (Residues: 9-236; Coverage: 31%)
Gene names: HSP90A, HSP90AA1, HSPC1, HSPCA
Sequence domains: Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
Structure domains: Histidine kinase-like ATPase, C-terminal domain

Ligands and Environments

1 bound ligand:
Ligand WOE 1 x WOE
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ENRAF-NONIUS FR591
Spacegroup: P21
Unit cell:
a: 54.196Å b: 44.126Å c: 53.263Å
α: 90° β: 115.65° γ: 90°
R-values:
R R work R free
0.196 0.194 0.223
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Propellanes-From a Chemical Curiosity to "Explosive" Materials and Natural Products.
Dilmaç et al. (2017)
1 more

1 mention without citation

Effective Estimation of Ligand-Binding Affinity Using Biased Sampling Method.
Ngo et al. (2019)