6ksq

From Proteopedia

(Difference between revisions)

Revision as of 09:13, 26 February 2020

Middle Domain of Human HSP90 Alpha

Structural highlights

6ksq is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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]

Publication Abstract from PubMed

Hsp90 is a target for anti-cancer drug development. Both the conformational events tuned by ATP/ADP and co-chaperones and the chaperoning cycle timing are required for Hsp90's fully functional display. Interfering with either one of the conformational events or the cycle timing will down-regulate Hsp90's function. In this manuscript, non-covalent allosteric modulators (SOMCL-16-171 and SOMCL-16-175) targeting Hsp90alpha's middle domain (Hsp90M) were developed for the first time. Multiple techniques were then applied to characterize the interactions between two active compounds and Hsp90alpha. Two loops and one alpha-helix (F349-N360, K443-E451, and D372-G387) in Hsp90M were identified responsible for the recognition of SOMCL-16-171 and SOMCL-16-175. Meanwhile, the binding of SOMCL-16-171 and SOMCL-16-175 to Hsp90M was demonstrated to allosterically modulate the structure and function of Hsp90alpha's N-terminal domain. Finally, cellular assays were conducted to evaluate the cellular activity of SOMCL-16-175, and the results indicate that SOMCL-16-175 destabilizes Hsp90's client proteins and reduces cell viability.

Allosteric Regulation of Hsp90alpha's Activity by Small Molecules Targeting the Middle Domain of the Chaperone.,Zhou C, Zhang C, Zhu H, Liu Z, Su H, Zhang X, Chen T, Zhong Y, Hu H, Xiong M, Zhou H, Xu Y, Zhang A, Zhang N iScience. 2020 Feb 21;23(2):100857. doi: 10.1016/j.isci.2020.100857. Epub 2020, Jan 21. PMID:32058968^[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
↑ Zhou C, Zhang C, Zhu H, Liu Z, Su H, Zhang X, Chen T, Zhong Y, Hu H, Xiong M, Zhou H, Xu Y, Zhang A, Zhang N. Allosteric Regulation of Hsp90alpha's Activity by Small Molecules Targeting the Middle Domain of the Chaperone. iScience. 2020 Feb 21;23(2):100857. doi: 10.1016/j.isci.2020.100857. Epub 2020, Jan 21. PMID:32058968 doi:http://dx.doi.org/10.1016/j.isci.2020.100857

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6ksq"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6ksq is ON HOLD  until Paper Publication
+==Middle Domain of Human HSP90 Alpha==
+<StructureSection load='6ksq' size='340' side='right'caption='[[6ksq]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6ksq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KSQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KSQ FirstGlance]. <br>
+</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=6ksq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ksq OCA], [http://pdbe.org/6ksq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ksq RCSB], [http://www.ebi.ac.uk/pdbsum/6ksq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ksq 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Hsp90 is a target for anti-cancer drug development. Both the conformational events tuned by ATP/ADP and co-chaperones and the chaperoning cycle timing are required for Hsp90's fully functional display. Interfering with either one of the conformational events or the cycle timing will down-regulate Hsp90's function. In this manuscript, non-covalent allosteric modulators (SOMCL-16-171 and SOMCL-16-175) targeting Hsp90alpha's middle domain (Hsp90M) were developed for the first time. Multiple techniques were then applied to characterize the interactions between two active compounds and Hsp90alpha. Two loops and one alpha-helix (F349-N360, K443-E451, and D372-G387) in Hsp90M were identified responsible for the recognition of SOMCL-16-171 and SOMCL-16-175. Meanwhile, the binding of SOMCL-16-171 and SOMCL-16-175 to Hsp90M was demonstrated to allosterically modulate the structure and function of Hsp90alpha's N-terminal domain. Finally, cellular assays were conducted to evaluate the cellular activity of SOMCL-16-175, and the results indicate that SOMCL-16-175 destabilizes Hsp90's client proteins and reduces cell viability.
-Authors:
+Allosteric Regulation of Hsp90alpha's Activity by Small Molecules Targeting the Middle Domain of the Chaperone.,Zhou C, Zhang C, Zhu H, Liu Z, Su H, Zhang X, Chen T, Zhong Y, Hu H, Xiong M, Zhou H, Xu Y, Zhang A, Zhang N iScience. 2020 Feb 21;23(2):100857. doi: 10.1016/j.isci.2020.100857. Epub 2020, Jan 21. PMID:32058968<ref>PMID:32058968</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6ksq" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Su, H X]]
+[[Category: Xu, Y C]]
+[[Category: Zhang, N X]]
+[[Category: Zhou, C]]
+[[Category: Chaperone]]
+[[Category: Hsp90]]

6ksq

From Proteopedia

Revision as of 09:13, 26 February 2020

Middle Domain of Human HSP90 Alpha

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox