1am1

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(Difference between revisions)

Revision as of 10:48, 15 November 2017

ATP BINDING SITE IN THE HSP90 MOLECULAR CHAPERONE

Structural highlights

1am1 is a 1 chain structure with sequence from Atcc 18824. The December 2008 RCSB PDB Molecule of the Month feature on Hsp90 by David Goodsell is 10.2210/rcsb_pdb/mom_2008_12. 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

[HSP82_YEAST] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. The nucleotide-free form of the dimer is found in an open conformation in which the N-termini are not dimerized and the complex is ready for client protein binding. Binding of ATP induces large conformational changes, resulting in the formation of a ring-like closed structure in which the N-terminal domains associate intramolecularly with the middle domain and also dimerize with each other, stimulating their intrinsic ATPase activity and acting as a clamp on the substrate. Finally, ATP hydrolysis results in the release of the substrate. 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. Required for growth at high temperatures.^[1]

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 molecular chaperones in eukaryotic cells play essential roles in the folding and activation of a range of client proteins involved in cell cycle regulation, steroid hormone responsiveness, and signal transduction. The biochemical mechanism of Hsp90 is poorly understood, and the involvement of ATP in particular is controversial. Crystal structures of complexes between the N-terminal domain of the yeast Hsp90 chaperone and ADP/ATP unambiguously identify a specific adenine nucleotide binding site homologous to the ATP-binding site of DNA gyrase B. This site is the same as that identified for the antitumor agent geldanamycin, suggesting that geldanamycin acts by blocking the binding of nucleotides to Hsp90 and not the binding of incompletely folded client polypeptides as previously suggested. These results finally resolve the question of the direct involvement of ATP in Hsp90 function.

Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone.,Prodromou C, Roe SM, O'Brien R, Ladbury JE, Piper PW, Pearl LH Cell. 1997 Jul 11;90(1):65-75. PMID:9230303^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Proisy N, Sharp SY, Boxall K, Connelly S, Roe SM, Prodromou C, Slawin AM, Pearl LH, Workman P, Moody CJ. Inhibition of Hsp90 with synthetic macrolactones: synthesis and structural and biological evaluation of ring and conformational analogs of radicicol. Chem Biol. 2006 Nov;13(11):1203-15. PMID:17114002 doi:10.1016/j.chembiol.2006.09.015
↑ Prodromou C, Roe SM, O'Brien R, Ladbury JE, Piper PW, Pearl LH. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell. 1997 Jul 11;90(1):65-75. PMID:9230303

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/1am1"

@@ Line 1: / Line 1: @@
 ==ATP BINDING SITE IN THE HSP90 MOLECULAR CHAPERONE==
 <StructureSection load='1am1' size='340' side='right' caption='[[1am1]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[1am1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. The December 2008 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Hsp90''  by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2008_12 10.2210/rcsb_pdb/mom_2008_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AM1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AM1 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</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=1am1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1am1 OCA], [http://pdbe.org/1am1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1am1 RCSB], [http://www.ebi.ac.uk/pdbsum/1am1 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=1am1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1am1 OCA], [http://pdbe.org/1am1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1am1 RCSB], [http://www.ebi.ac.uk/pdbsum/1am1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1am1 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 30: / Line 31: @@
 ==See Also==
 *[[Chaperones|Chaperones]]
-*[[Heat Shock Proteins|Heat Shock Proteins]]
 == References ==
 <references/>

1am1

From Proteopedia

Revision as of 10:48, 15 November 2017

ATP BINDING SITE IN THE HSP90 MOLECULAR CHAPERONE

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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