3qdd

From Proteopedia

(Difference between revisions)

Revision as of 13:35, 4 August 2016

HSP90A N-terminal domain in complex with BIIB021

Structural highlights

3qdd 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:
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

Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3 -d]pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that completed phase II clinical trials. Alkyne 40 is more potent than 14 in an Hsp90alpha binding assay (IC(50) = 1.1 vs 5.1 nM) as well as in its ability to degrade Her-2 in MCF-7 cells (EC(50) = 14 vs 38 nM). In a mouse model of gastric tumors (N87), 40 stops tumor growth at 5 mg/kg and causes partial tumor regressions at 10 mg/kg (po, qdx5). Under the same conditions, 14 stops tumor growth only at 120 mg/kg, and does not induce partial regressions. Thus, alkyne 40 is approximately 20-fold more efficacious than 14 in mice.

EC144 Is a Potent Inhibitor of the Heat Shock Protein 90.,Shi J, Van de Water R, Hong K, Lamer RB, Weichert KW, Sandoval CM, Kasibhatla SR, Boehm MF, Chao J, Lundgren K, Timple N, Lough R, Ibanez G, Boykin C, Burrows FJ, Kehry MR, Yun TJ, Harning EK, Ambrose C, Thompson J, Bixler SA, Dunah A, Snodgrass-Belt P, Arndt J, Enyedy IJ, Li P, Hong VS, McKenzie A, Biamonte MA J Med Chem. 2012 Sep 13;55(17):7786-95. Epub 2012 Aug 31. PMID:22938030^[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
↑ Shi J, Van de Water R, Hong K, Lamer RB, Weichert KW, Sandoval CM, Kasibhatla SR, Boehm MF, Chao J, Lundgren K, Timple N, Lough R, Ibanez G, Boykin C, Burrows FJ, Kehry MR, Yun TJ, Harning EK, Ambrose C, Thompson J, Bixler SA, Dunah A, Snodgrass-Belt P, Arndt J, Enyedy IJ, Li P, Hong VS, McKenzie A, Biamonte MA. EC144 Is a Potent Inhibitor of the Heat Shock Protein 90. J Med Chem. 2012 Sep 13;55(17):7786-95. Epub 2012 Aug 31. PMID:22938030 doi:http://dx.doi.org/10.1021/jm300810x

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/3qdd"

Categories: Human | Arndt, J W | Biamonte, M A | Atpase | Chaperone-chaperone inhibitor complex

@@ Line 1: / Line 1: @@
 ==HSP90A N-terminal domain in complex with BIIB021==
 <StructureSection load='3qdd' size='340' side='right' caption='[[3qdd]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3qdd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QDD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QDD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3qdd]] 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=3QDD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QDD FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=94M:6-CHLORO-9-[(4-METHOXY-3,5-DIMETHYLPYRIDIN-2-YL)METHYL]-9H-PURIN-2-AMINE'>94M</scene></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 Homo sapiens])</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=3qdd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qdd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qdd RCSB], [http://www.ebi.ac.uk/pdbsum/3qdd 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=3qdd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qdd OCA], [http://pdbe.org/3qdd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qdd RCSB], [http://www.ebi.ac.uk/pdbsum/3qdd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qdd ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3qdd" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Arndt, J W]]
 [[Category: Biamonte, M A]]
 [[Category: Atpase]]
 [[Category: Chaperone-chaperone inhibitor complex]]

3qdd

From Proteopedia

Revision as of 13:35, 4 August 2016

HSP90A N-terminal domain in complex with BIIB021

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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