1yc4

From Proteopedia

(Difference between revisions)

Revision as of 18:05, 25 December 2014

Crystal structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles

Structural highlights

1yc4 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1yc1, 1yc3
Gene:	HSPCA, HSP90A, HSPC1 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

A series of dihydroxyphenylpyrazole compounds were identified as a unique class of reversible Hsp90 inhibitors. The crystal structures for two of the identified compounds complexed with the N-terminal ATP binding domain of human Hsp90alpha were determined. The dihydroxyphenyl ring of the compounds fits deeply into the adenine binding pocket with the C2 hydroxyl group forming a direct hydrogen bond with the side chain of Asp93. The pyrazole ring forms hydrogen bonds to the backbone carbonyl of Gly97, the hydroxyl group of Thr184 and to a water molecule, which is present in all of the published HSP90 structures. One of the identified compounds (G3130) demonstrated cellular activities (in Her-2 degradation and activation of Hsp70 promoter) consistent with the inhibition of cellular Hsp90 functions.

Crystal structures of human HSP90alpha-complexed with dihydroxyphenylpyrazoles.,Kreusch A, Han S, Brinker A, Zhou V, Choi HS, He Y, Lesley SA, Caldwell J, Gu XJ Bioorg Med Chem Lett. 2005 Mar 1;15(5):1475-8. PMID:15713410^[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
↑ Kreusch A, Han S, Brinker A, Zhou V, Choi HS, He Y, Lesley SA, Caldwell J, Gu XJ. Crystal structures of human HSP90alpha-complexed with dihydroxyphenylpyrazoles. Bioorg Med Chem Lett. 2005 Mar 1;15(5):1475-8. PMID:15713410 doi:10.1016/j.bmcl.2004.12.087

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1yc4"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1yc4]] 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=1YC4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1YC4 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=43P:4-(1H-IMIDAZOL-4-YL)-3-(5-ETHYL-2,4-DIHYDROXY-PHENYL)-1H-PYRAZOLE'>43P</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=43P:4-(1H-IMIDAZOL-4-YL)-3-(5-ETHYL-2,4-DIHYDROXY-PHENYL)-1H-PYRAZOLE'>43P</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1yc1|1yc1]], [[1yc3|1yc3]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1yc1|1yc1]], [[1yc3|1yc3]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSPCA, HSP90A, HSPC1 ([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">HSPCA, HSP90A, HSPC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yc4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1yc4 RCSB], [http://www.ebi.ac.uk/pdbsum/1yc4 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=1yc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yc4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1yc4 RCSB], [http://www.ebi.ac.uk/pdbsum/1yc4 PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/HS90A_HUMAN 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.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 34: / Line 36: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Brinker, A.]]
+[[Category: Brinker, A]]
-[[Category: Caldwell, J.]]
+[[Category: Caldwell, J]]
-[[Category: Choi, H.]]
+[[Category: Choi, H]]
-[[Category: Gu, X.]]
+[[Category: Gu, X]]
-[[Category: Han, S.]]
+[[Category: Han, S]]
-[[Category: He, Y.]]
+[[Category: He, Y]]
-[[Category: Kreusch, A.]]
+[[Category: Kreusch, A]]
-[[Category: Lesley, S A.]]
+[[Category: Lesley, S A]]
-[[Category: Zhou, V.]]
+[[Category: Zhou, V]]
 [[Category: Cancer]]
 [[Category: Cell cycle]]
 [[Category: Cell-cycle]]
 [[Category: Drug design]]

1yc4

From Proteopedia

Revision as of 18:05, 25 December 2014

Crystal structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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