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3rlr

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Revision as of 11:04, 11 August 2016

Co-crystal structure of the HSP90 ATP binding domain in complex with 4-(2,4-dichloro-5-methoxyphenyl)-2,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile

Structural highlights

3rlr is a 2 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:	3rlp, 3rlq
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

A series of novel and potent small molecule Hsp90 inhibitors was optimized using X-ray crystal structures. These compounds bind in a deep pocket of the Hsp90 enzyme that is partially comprised by residues Asn51 and Ser52. Displacement of several water molecules observed crystallographically in this pocket using rule-based strategies led to significant improvements in inhibitor potency. An optimized inhibitor (compound 17) exhibited potent Hsp90 inhibition in ITC, biochemical, and cell-based assays (K(d)=1.3nM, K(i)=15nM, and cellular IC(50)=0.5muM).

Design strategies to target crystallographic waters applied to the Hsp90 molecular chaperone.,Kung PP, Sinnema PJ, Richardson P, Hickey MJ, Gajiwala KS, Wang F, Huang B, McClellan G, Wang J, Maegley K, Bergqvist S, Mehta PP, Kania R Bioorg Med Chem Lett. 2011 Jun 15;21(12):3557-62. Epub 2011 May 5. PMID:21612924^[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
↑ Kung PP, Sinnema PJ, Richardson P, Hickey MJ, Gajiwala KS, Wang F, Huang B, McClellan G, Wang J, Maegley K, Bergqvist S, Mehta PP, Kania R. Design strategies to target crystallographic waters applied to the Hsp90 molecular chaperone. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3557-62. Epub 2011 May 5. PMID:21612924 doi:10.1016/j.bmcl.2011.04.130

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/3rlr"

@@ Line 1: / Line 1: @@
 ==Co-crystal structure of the HSP90 ATP binding domain in complex with 4-(2,4-dichloro-5-methoxyphenyl)-2,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile==
 <StructureSection load='3rlr' size='340' side='right' caption='[[3rlr]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rlp|3rlp]], [[3rlq|3rlq]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, HSPC1, HSPCA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3rlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rlr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rlr RCSB], [http://www.ebi.ac.uk/pdbsum/3rlr PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3rlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rlr OCA], [http://pdbe.org/3rlr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rlr RCSB], [http://www.ebi.ac.uk/pdbsum/3rlr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rlr ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3rlr" style="background-color:#fffaf0;"></div>
 ==See Also==

3rlr

From Proteopedia

Revision as of 11:04, 11 August 2016

Co-crystal structure of the HSP90 ATP binding domain in complex with 4-(2,4-dichloro-5-methoxyphenyl)-2,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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