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1osf

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Revision as of 07:59, 15 February 2018

Human Hsp90 in complex with 17-desmethoxy-17-N,N-Dimethylaminoethylamino-Geldanamycin

Structural highlights

1osf is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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

Hsp90 is an attractive chemotherapeutic target because it chaperones the folding of proteins found in multiple signal transduction pathways. We describe the 1.75 A resolution crystal structure of human Hsp90 alpha (residues 9-236) complexed with 17-desmethoxy-17-N,N-dimethylaminoethylamino-geldanamycin (17-DMAG). The structure revealed an altered set of interactions between the 17-substituent and the protein compared to geldanamycin and the 17-dimethylaminoethyl moiety pointing into solvent, but otherwise was similar to that reported for the complex with geldanamycin. Targeted molecular dynamics simulations and energetic analysis indicate that geldanamycin undergoes two major conformational changes when it binds Hsp90, with the key step of the conversion being the trans to cis conformational change of the macrocycle amide bond. We speculate that 17-DMAG analogs constrained to a cis-amide in the ground state could provide a significant increase in affinity for Hsp90.

Crystal structure and molecular modeling of 17-DMAG in complex with human Hsp90.,Jez JM, Chen JC, Rastelli G, Stroud RM, Santi DV Chem Biol. 2003 Apr;10(4):361-8. PMID:12725864^[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
↑ Jez JM, Chen JC, Rastelli G, Stroud RM, Santi DV. Crystal structure and molecular modeling of 17-DMAG in complex with human Hsp90. Chem Biol. 2003 Apr;10(4):361-8. PMID:12725864

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Human Hsp90 in complex with 17-desmethoxy-17-N,N-Dimethylaminoethylamino-Geldanamycin==
 <StructureSection load='1osf' size='340' side='right' caption='[[1osf]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[1osf]] 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=1OSF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OSF FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=KOS:17-DESMETHOXY-17-N,N-DIMETHYLAMINOETHYLAMINO-GELDANAMYCIN'>KOS</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=1osf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osf OCA], [http://pdbe.org/1osf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1osf RCSB], [http://www.ebi.ac.uk/pdbsum/1osf 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=1osf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osf OCA], [http://pdbe.org/1osf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1osf RCSB], [http://www.ebi.ac.uk/pdbsum/1osf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1osf ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 12: / Line 13: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/os/1osf_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/os/1osf_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 27: / Line 28: @@
 </div>
 <div class="pdbe-citations 1osf" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Heat Shock Proteins|Heat Shock Proteins]]
 == References ==
 <references/>

1osf

From Proteopedia

Revision as of 07:59, 15 February 2018

Human Hsp90 in complex with 17-desmethoxy-17-N,N-Dimethylaminoethylamino-Geldanamycin

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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