3owb

Crystal Structure of HSP90 with VER-49009Crystal Structure of HSP90 with VER-49009

Structural highlights

3owb is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3ow6, 3owd
Gene:	HSP90AA1, HSP90A, HSPC1, HSPCA (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.^[1] ^[2]

Publication Abstract from PubMed

We describe the development of a novel series of N-aryl-benzimidazolone HSP90 inhibitors (9) targeting the N-terminal ATP-ase site. SAR development was influenced by structure-based design based around X-ray structures of ligand bound HSP90 complexes. Lead compounds exhibited high binding affinities, ATP-ase inhibition and cellular client protein degradation.

N-aryl-benzimidazolones as novel small molecule HSP90 inhibitors.,Bruncko M, Tahir SK, Song X, Chen J, Ding H, Huth JR, Jin S, Judge RA, Madar DJ, Park CH, Park CM, Petros AM, Tse C, Rosenberg SH, Elmore SW Bioorg Med Chem Lett. 2010 Dec 15;20(24):7503-6. Epub 2010 Oct 12. PMID:21106457^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Martinez-Ruiz A, Villanueva L, Gonzalez de Orduna C, Lopez-Ferrer D, Higueras MA, Tarin C, Rodriguez-Crespo I, Vazquez J, Lamas S. S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8525-30. Epub 2005 Jun 3. PMID:15937123 doi:10.1073/pnas.0407294102
↑ Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE. Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem. 2001 May 11;276(19):15571-4. Epub 2001 Mar 23. PMID:11274138 doi:10.1074/jbc.C100055200
↑ Bruncko M, Tahir SK, Song X, Chen J, Ding H, Huth JR, Jin S, Judge RA, Madar DJ, Park CH, Park CM, Petros AM, Tse C, Rosenberg SH, Elmore SW. N-aryl-benzimidazolones as novel small molecule HSP90 inhibitors. Bioorg Med Chem Lett. 2010 Dec 15;20(24):7503-6. Epub 2010 Oct 12. PMID:21106457 doi:10.1016/j.bmcl.2010.10.010

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OCA

[1] Martinez-Ruiz A, Villanueva L, Gonzalez de Orduna C, Lopez-Ferrer D, Higueras MA, Tarin C, Rodriguez-Crespo I, Vazquez J, Lamas S. S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8525-30. Epub 2005 Jun 3. PMID:15937123 doi:10.1073/pnas.0407294102

[2] Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE. Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem. 2001 May 11;276(19):15571-4. Epub 2001 Mar 23. PMID:11274138 doi:10.1074/jbc.C100055200

[3] Bruncko M, Tahir SK, Song X, Chen J, Ding H, Huth JR, Jin S, Judge RA, Madar DJ, Park CH, Park CM, Petros AM, Tse C, Rosenberg SH, Elmore SW. N-aryl-benzimidazolones as novel small molecule HSP90 inhibitors. Bioorg Med Chem Lett. 2010 Dec 15;20(24):7503-6. Epub 2010 Oct 12. PMID:21106457 doi:10.1016/j.bmcl.2010.10.010

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