4bqj

From Proteopedia

(Difference between revisions)

Revision as of 08:59, 3 August 2017

structure of HSP90 with an inhibitor bound

Structural highlights

4bqj is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4bqg
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

Novel small molecule inhibitors of heat shock protein 90 (Hsp90) were discovered with the help of a fragment based drug discovery approach (FBDD) and subsequent optimization with a combination of structure guided design, parallel synthesis and application of medicinal chemistry principles. These efforts led to the identification of compound 18 (NMS-E973), which displayed significant efficacy in a human ovarian A2780 xenograft tumor model, with a mechanism of action confirmed in vivo by typical modulation of known Hsp90 client proteins, and with a favorable pharmacokinetic and safety profile.

Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock protein 90 (Hsp90).,Brasca MG, Mantegani S, Amboldi N, Bindi S, Caronni D, Casale E, Ceccarelli W, Colombo N, De Ponti A, Donati D, Ermoli A, Fachin G, Felder ER, Ferguson RD, Fiorelli C, Guanci M, Isacchi A, Pesenti E, Polucci P, Riceputi L, Sola F, Visco C, Zuccotto F, Fogliatto G Bioorg Med Chem. 2013 Nov 15;21(22):7047-63. doi: 10.1016/j.bmc.2013.09.018. Epub, 2013 Sep 19. PMID:24100158^[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
↑ Brasca MG, Mantegani S, Amboldi N, Bindi S, Caronni D, Casale E, Ceccarelli W, Colombo N, De Ponti A, Donati D, Ermoli A, Fachin G, Felder ER, Ferguson RD, Fiorelli C, Guanci M, Isacchi A, Pesenti E, Polucci P, Riceputi L, Sola F, Visco C, Zuccotto F, Fogliatto G. Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock protein 90 (Hsp90). Bioorg Med Chem. 2013 Nov 15;21(22):7047-63. doi: 10.1016/j.bmc.2013.09.018. Epub, 2013 Sep 19. PMID:24100158 doi:http://dx.doi.org/10.1016/j.bmc.2013.09.018

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4bqj"

@@ Line 3: / Line 3: @@
 <StructureSection load='4bqj' size='340' side='right' caption='[[4bqj]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4bqj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BQJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BQJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4bqj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BQJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BQJ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=XKL:5-[2,4-DIHYDROXY-6-(4-NITROPHENOXY)PHENYL]-N-ETHYL-1,2-OXAZOLE-3-CARBOXAMIDE'>XKL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bqg|4bqg]]</td></tr>
@@ Line 26: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
 [[Category: Amboldi, N]]
 [[Category: Bindi, S]]

4bqj

From Proteopedia

Revision as of 08:59, 3 August 2017

structure of HSP90 with an inhibitor bound

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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