› 3r92

X-ray diffraction
1.58Å resolution

Discovery of a macrocyclic o-aminobenzamide Hsp90 inhibitor with heterocyclic tether that shows extended biomarker activity and in vivo efficacy in a mouse xenograft model.

Released:
DOI: 10.2210/pdb3r92/pdb
PDB entry 3r92 coloured by chain, front view.
PDB entry 3r92 coloured by chain, side view.
PDB entry 3r92 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of a macrocyclic o-aminobenzamide Hsp90 inhibitor with heterocyclic tether that shows extended biomarker activity and in vivo efficacy in a mouse xenograft model.
Zapf CW, Bloom JD, McBean JL, Dushin RG, Golas JM, Liu H, Lucas J, Boschelli F, Vogan E, Levin JI
Bioorg Med Chem Lett 21 3627-31 (2011)
PMID: 21605975

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: 226 amino acids
Theoretical weight: 25.41 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P07900 (Residues: 10-236; 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 06J 1 x 06J
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E+ SUPERBRIGHT
Spacegroup: I222
Unit cell:
a: 67.35Å b: 90.355Å c: 98.594Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.177 0.176 0.194
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

2 review citations

Macrocyclic drugs and synthetic methodologies toward macrocycles.
Yu et al. (2013)
1 more