2bt0

From Proteopedia

(Difference between revisions)

Current revision

Novel, potent small molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design

Structural highlights

2bt0 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Ligands:
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

The crystal structure of a previously reported screening hit 1 (CCT018159) bound to the N terminal domain of molecular chaperone Hsp90 has been used to design 5-amide analogues. These exhibit enhanced potency against the target in binding and functional assays with accompanying appropriate cellular pharmacodynamic changes. Compound 11 (VER-49009) compares favorably with the clinically evaluated 17-AAG.

Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design.,Dymock BW, Barril X, Brough PA, Cansfield JE, Massey A, McDonald E, Hubbard RE, Surgenor A, Roughley SD, Webb P, Workman P, Wright L, Drysdale MJ J Med Chem. 2005 Jun 30;48(13):4212-5. PMID:15974572^[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
↑ Dymock BW, Barril X, Brough PA, Cansfield JE, Massey A, McDonald E, Hubbard RE, Surgenor A, Roughley SD, Webb P, Workman P, Wright L, Drysdale MJ. Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design. J Med Chem. 2005 Jun 30;48(13):4212-5. PMID:15974572 doi:10.1021/jm050355z

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/2bt0"

@@ Line 1: / Line 1: @@
 ==Novel, potent small molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design==
-<StructureSection load='2bt0' size='340' side='right' caption='[[2bt0]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='2bt0' size='340' side='right'caption='[[2bt0]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2bt0]] is a 2 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=2BT0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BT0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2bt0]] 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=2BT0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BT0 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CT5:4-[4-(2,3-DIHYDRO-1,4-BENZODIOXIN-6-YL)-3-METHYL-1H-PYRAZOL-5-YL]-6-ETHYLBENZENE-1,3-DIOL'>CT5</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]] 1.9&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[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]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CT5:4-[4-(2,3-DIHYDRO-1,4-BENZODIOXIN-6-YL)-3-METHYL-1H-PYRAZOL-5-YL]-6-ETHYLBENZENE-1,3-DIOL'>CT5</scene></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=2bt0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bt0 OCA], [http://pdbe.org/2bt0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bt0 RCSB], [http://www.ebi.ac.uk/pdbsum/2bt0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2bt0 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=2bt0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bt0 OCA], [https://pdbe.org/2bt0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bt0 RCSB], [https://www.ebi.ac.uk/pdbsum/2bt0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bt0 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 29: / Line 29: @@
 </div>
 <div class="pdbe-citations 2bt0" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Heat Shock Protein structures|Heat Shock Protein structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Barril, X]]
+[[Category: Large Structures]]
-[[Category: Brough, P A]]
+[[Category: Barril X]]
-[[Category: Cansfield, J E]]
+[[Category: Brough PA]]
-[[Category: Drysdale, M J]]
+[[Category: Cansfield JE]]
-[[Category: Dymock, B W]]
+[[Category: Drysdale MJ]]
-[[Category: Hubbard, R E]]
+[[Category: Dymock BW]]
-[[Category: Massey, A]]
+[[Category: Hubbard RE]]
-[[Category: McDonald, E]]
+[[Category: Massey A]]
-[[Category: Roughley, S D]]
+[[Category: McDonald E]]
-[[Category: Surgenor, A]]
+[[Category: Roughley SD]]
-[[Category: Webb, P]]
+[[Category: Surgenor A]]
-[[Category: Workman, P]]
+[[Category: Webb P]]
-[[Category: Wright, L]]
+[[Category: Workman P]]
-[[Category: Atp-binding]]
+[[Category: Wright L]]
-[[Category: Chaperone]]
-[[Category: Heat shock]]
-[[Category: Phosphorylation]]

2bt0

From Proteopedia

Current revision

Novel, potent small molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design

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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