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| | <StructureSection load='4r3m' size='340' side='right'caption='[[4r3m]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='4r3m' size='340' side='right'caption='[[4r3m]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4r3m]] 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=4R3M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R3M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4r3m]] 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=4R3M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R3M FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JR9:N~3~-BENZYL-2-[(6-BROMO-1,3-BENZODIOXOL-5-YL)METHYL]IMIDAZO[1,2-A]PYRAZINE-3,8-DIAMINE'>JR9</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JR9:N~3~-BENZYL-2-[(6-BROMO-1,3-BENZODIOXOL-5-YL)METHYL]IMIDAZO[1,2-A]PYRAZINE-3,8-DIAMINE'>JR9</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90A, HSP90AA1, 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'>[https://proteopedia.org/fgij/fg.htm?mol=4r3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r3m OCA], [https://pdbe.org/4r3m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r3m RCSB], [https://www.ebi.ac.uk/pdbsum/4r3m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r3m ProSAT]</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=4r3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r3m OCA], [http://pdbe.org/4r3m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r3m RCSB], [http://www.ebi.ac.uk/pdbsum/4r3m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r3m ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Heat Shock Proteins|Heat Shock Proteins]] | + | *[[Heat Shock Protein structures|Heat Shock Protein structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: He, J]] | + | [[Category: He J]] |
| - | [[Category: Li, J]] | + | [[Category: Li J]] |
| - | [[Category: Ren, J]] | + | [[Category: Ren J]] |
| - | [[Category: Xiong, B]] | + | [[Category: Xiong B]] |
| - | [[Category: Yang, M]] | + | [[Category: Yang M]] |
| - | [[Category: Chaperone-chaperone inhibitor complex]]
| + | |
| - | [[Category: Chaperone/chaperone inhibitor]]
| + | |
| Structural highlights
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
Using a 2,3-diamino pyrazine substrate and yttrium triflate catalyst, various 2-alkyl and aryl substituted 3,8-diaminoimidazo[1,2-a]pyrazines were efficiently prepared through Groebke-Blackburn-Bienayme MCR. In particular, a novel 2-piperonyl 3,8-diaminoimidazo[1,2-a]pyrazine structure was prepared exclusively with this new method and was found to have moderate Hsp90 inhibitory activity. A crystalline complex with N-terminus ATP domain of Hsp90 and one of the new Hsp90 inhibitors was also obtained to elucidate the origin of activity of 2-piperonyl 3,8-diaminoimidazo[1,2-a]pyrazines.
Multi-substituted 8-aminoimidazo[1,2-a]pyrazines by Groebke-Blackburn-Bienayme reaction and their Hsp90 inhibitory activity.,Ren J, Yang M, Liu H, Cao D, Chen D, Li J, Tang L, He J, Chen YL, Geng M, Xiong B, Shen J Org Biomol Chem. 2015 Feb 7;13(5):1531-5. doi: 10.1039/c4ob01865f. PMID:25490978[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Ren J, Yang M, Liu H, Cao D, Chen D, Li J, Tang L, He J, Chen YL, Geng M, Xiong B, Shen J. Multi-substituted 8-aminoimidazo[1,2-a]pyrazines by Groebke-Blackburn-Bienayme reaction and their Hsp90 inhibitory activity. Org Biomol Chem. 2015 Feb 7;13(5):1531-5. doi: 10.1039/c4ob01865f. PMID:25490978 doi:http://dx.doi.org/10.1039/c4ob01865f
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