3bm9: Difference between revisions

Revision as of 08:19, 19 January 2022

Discovery of Benzisoxazoles as Potent Inhibitors of Chaperone Hsp90

Structural highlights

3bm9 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:	BXZ
Related:	3bmy
Gene:	HSP90AA1, HSP90A, HSPC1, HSPCA (Homo sapiens)
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]

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

Heat shock protein 90 (Hsp90) is a molecular chaperone that is responsible for activating many signaling proteins and is a promising target in tumor biology. We have identified small-molecule benzisoxazole derivatives as Hsp90 inhibitors. Crystallographic studies show that these compounds bind in the ATP binding pocket interacting with the Asp93. Structure based optimization led to the identification of potent analogues, such as 13, with good biochemical profiles.

Discovery of benzisoxazoles as potent inhibitors of chaperone heat shock protein 90.,Gopalsamy A, Shi M, Golas J, Vogan E, Jacob J, Johnson M, Lee F, Nilakantan R, Petersen R, Svenson K, Chopra R, Tam MS, Wen Y, Ellingboe J, Arndt K, Boschelli F J Med Chem. 2008 Feb 14;51(3):373-5. Epub 2008 Jan 16. PMID:18197612^[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
↑ Gopalsamy A, Shi M, Golas J, Vogan E, Jacob J, Johnson M, Lee F, Nilakantan R, Petersen R, Svenson K, Chopra R, Tam MS, Wen Y, Ellingboe J, Arndt K, Boschelli F. Discovery of benzisoxazoles as potent inhibitors of chaperone heat shock protein 90. J Med Chem. 2008 Feb 14;51(3):373-5. Epub 2008 Jan 16. PMID:18197612 doi:10.1021/jm701385c

Proteopedia Page Contributors and Editors (what is this?)

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] Gopalsamy A, Shi M, Golas J, Vogan E, Jacob J, Johnson M, Lee F, Nilakantan R, Petersen R, Svenson K, Chopra R, Tam MS, Wen Y, Ellingboe J, Arndt K, Boschelli F. Discovery of benzisoxazoles as potent inhibitors of chaperone heat shock protein 90. J Med Chem. 2008 Feb 14;51(3):373-5. Epub 2008 Jan 16. PMID:18197612 doi:10.1021/jm701385c

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
 ==Discovery of Benzisoxazoles as Potent Inhibitors of Chaperone Hsp90==
-<StructureSection load='3bm9' size='340' side='right' caption='[[3bm9]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+<StructureSection load='3bm9' size='340' side='right'caption='[[3bm9]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3bm9]] 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=3BM9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BM9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3bm9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BM9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BXZ:4-BROMO-6-(6-HYDROXY-1,2-BENZISOXAZOL-3-YL)BENZENE-1,3-DIOL'>BXZ</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BXZ:4-BROMO-6-(6-HYDROXY-1,2-BENZISOXAZOL-3-YL)BENZENE-1,3-DIOL'>BXZ</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bmy|3bmy]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3bmy|3bmy]]</div></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 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3bm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bm9 OCA], [http://pdbe.org/3bm9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bm9 RCSB], [http://www.ebi.ac.uk/pdbsum/3bm9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3bm9 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bm9 OCA], [https://pdbe.org/3bm9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bm9 RCSB], [https://www.ebi.ac.uk/pdbsum/3bm9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bm9 ProSAT]</span></td></tr>
 </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>
+[[https://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 32: / Line 32: @@
 ==See Also==
-*[[Heat Shock Proteins|Heat Shock Proteins]]
+*[[Heat Shock Protein structures|Heat Shock Protein structures]]
 == References ==
 <references/>
@@ Line 38: / Line 38: @@
 </StructureSection>
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Arndt, K]]
 [[Category: Boschelli, F]]

3bm9: Difference between revisions

Revision as of 08:19, 19 January 2022

Discovery of Benzisoxazoles as Potent Inhibitors of Chaperone Hsp90

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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