4NH8: Correlation between chemotype-dependent binding conformations of HSP90 alpha/beta and isoform selectivity

HSP90 continues to be a target of interest for neurodegeneration indications. Selective knockdown of the HSP90 cytosolic isoforms alpha and beta is sufficient to reduce mutant huntingtin protein levels in vitro. Chemotype-dependent binding conformations of HSP90alpha/beta appear to strongly influence isoform selectivity. The rational design of HSP90alpha/beta inhibitors selective versus the mitochondrial (TRAP1) and endoplasmic reticulum (GRP94) isoforms offers a potential mitigating strategy for mechanism-based toxicities. Better tolerated HSP90 inhibitors would be attractive for targeting chronic neurodegenerative diseases such as Huntington's disease.
PDB ID: 4NH8Download
MMDB ID: 116699
PDB Deposition Date: 2013/11/4
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.65  Å
Source Organism:
Similar Structures:
Biological Unit for 4NH8: monomeric; determined by author
Molecular Components in 4NH8
Label Count Molecule
Protein (1 molecule)
Heat Shock Protein HSP 90-alpha(Gene symbol: HSP90AA1)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB