› 4fcq

X-ray diffraction
2.15Å resolution

Targeting conserved water molecules: Design of 4-aryl-5-cyanopyrrolo[2,3-d]pyrimidine Hsp90 inhibitors using fragment-based screening and structure-based optimization

Released:
DOI: 10.2210/pdb4fcq/pdb
PDB entry 4fcq coloured by chain, front view.
PDB entry 4fcq coloured by chain, side view.
PDB entry 4fcq coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Targeting conserved water molecules: design of 4-aryl-5-cyanopyrrolo[2,3-d]pyrimidine Hsp90 inhibitors using fragment-based screening and structure-based optimization.
Davies NG, Browne H, Davis B, Drysdale MJ, Foloppe N, Geoffrey S, Gibbons B, Hart T, Hubbard R, Jensen MR, Mansell H, Massey A, Matassova N, Moore JD, Murray J, Pratt R, Ray S, Robertson A, Roughley SD, Schoepfer J, Scriven K, Simmonite H, Stokes S, Surgenor A, Webb P, Wood M, Wright L, Brough P
Bioorg Med Chem 20 6770-89 (2012)
PMID: 23018093

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

Assemblies composition:
monomeric (preferred)
homo dimer
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: 236 amino acids
Theoretical weight: 26.6 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P07900 (Residues: 1-236; Coverage: 32%)
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 2N6 1 x 2N6
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID29
Spacegroup: I222
Unit cell:
a: 64.976Å b: 87.957Å c: 99.205Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.247 0.188 0.247
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

5 review citations

Current progress in Structure-Based Rational Drug Design marks a new mindset in drug discovery.
Lounnas et al. (2013)
4 more

1 mention without citation

Accounting for the Central Role of Interfacial Water in Protein-Ligand Binding Free Energy Calculations.
Ben-Shalom et al. (2020)