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| | <StructureSection load='2bz5' size='340' side='right'caption='[[2bz5]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='2bz5' size='340' side='right'caption='[[2bz5]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2bz5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BZ5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2bz5]] is a 2 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=2BZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BZ5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AB4:2,5-DICHLORO-N-[4-HYDROXY-3-(2-HYDROXY-1-NAPHTHYL)PHENYL]BENZENESULFONAMIDE'>AB4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1byq|1byq]], [[1osf|1osf]], [[1uy6|1uy6]], [[1uy7|1uy7]], [[1uy8|1uy8]], [[1uy9|1uy9]], [[1uyc|1uyc]], [[1uyd|1uyd]], [[1uye|1uye]], [[1uyf|1uyf]], [[1uyg|1uyg]], [[1uyh|1uyh]], [[1uyi|1uyi]], [[1uyk|1uyk]], [[1uyl|1uyl]], [[1yc1|1yc1]], [[1yc3|1yc3]], [[1yc4|1yc4]], [[1yer|1yer]], [[1yes|1yes]], [[1yet|1yet]], [[2bsm|2bsm]], [[2bt0|2bt0]], [[2byh|2byh]], [[2byi|2byi]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AB4:2,5-DICHLORO-N-[4-HYDROXY-3-(2-HYDROXY-1-NAPHTHYL)PHENYL]BENZENESULFONAMIDE'>AB4</scene></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=2bz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bz5 OCA], [https://pdbe.org/2bz5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bz5 RCSB], [https://www.ebi.ac.uk/pdbsum/2bz5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bz5 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=2bz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bz5 OCA], [https://pdbe.org/2bz5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bz5 RCSB], [https://www.ebi.ac.uk/pdbsum/2bz5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bz5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Barril, X]] | + | [[Category: Barril X]] |
| - | [[Category: Brough, P]] | + | [[Category: Brough P]] |
| - | [[Category: Drysdale, M]] | + | [[Category: Drysdale M]] |
| - | [[Category: Hubbard, R E]] | + | [[Category: Hubbard RE]] |
| - | [[Category: Massey, A]] | + | [[Category: Massey A]] |
| - | [[Category: Surgenor, A]] | + | [[Category: Surgenor A]] |
| - | [[Category: Wright, L]] | + | [[Category: Wright L]] |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Heat shock]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| 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]
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
Docking-based virtual screening identified 1-(2-phenol)-2-naphthol compounds as a new class of Hsp90 inhibitors of low to sub-micromolar potency. Here we report the binding affinities and cellular activities of several members of this class. A high resolution crystal structure of the most potent compound reveals its binding mode in the ATP binding site of Hsp90, providing a rationale for the observed activity of the series and suggesting strategies for developing compounds with improved properties.
Structure-based discovery of a new class of Hsp90 inhibitors.,Barril X, Brough P, Drysdale M, Hubbard RE, Massey A, Surgenor A, Wright L Bioorg Med Chem Lett. 2005 Dec 1;15(23):5187-91. Epub 2005 Oct 3. PMID:16202589[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
- ↑ Barril X, Brough P, Drysdale M, Hubbard RE, Massey A, Surgenor A, Wright L. Structure-based discovery of a new class of Hsp90 inhibitors. Bioorg Med Chem Lett. 2005 Dec 1;15(23):5187-91. Epub 2005 Oct 3. PMID:16202589 doi:10.1016/j.bmcl.2005.08.092
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