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3b28

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Revision as of 11:21, 5 January 2022

Hsp90 alpha N-terminal domain in complex with an inhibitor CH5015765

Structural highlights

3b28 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	3b24, 3b25, 3b26, 3b27
Gene:	HSP90AA1 (HUMAN)
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

Heat shock protein 90 (Hsp90) is a molecular chaperone which regulates maturation and stabilization of its substrate proteins, known as client proteins. Many client proteins of Hsp90 are involved in tumor progression and survival and therefore Hsp90 can be a good target for developing anticancer drugs. With the aim of efficiently identifying a new class of orally available inhibitors of the ATP binding site of this protein, we conducted fragment screening and virtual screening in parallel against Hsp90. This approach quickly identified 2-aminotriazine and 2-aminopyrimidine derivatives as specific ligands to Hsp90 with high ligand efficiency. In silico evaluation of the 3D X-ray Hsp90 complex structures of the identified hits allowed us to promptly design CH5015765, which showed high affinity for Hsp90 and antitumor activity in human cancer xenograft mouse models.

Lead generation of heat shock protein 90 inhibitors by a combination of fragment-based approach, virtual screening, and structure-based drug design.,Miura T, Fukami TA, Hasegawa K, Ono N, Suda A, Shindo H, Yoon DO, Kim SJ, Na YJ, Aoki Y, Shimma N, Tsukuda T, Shiratori Y Bioorg Med Chem Lett. 2011 Oct 1;21(19):5778-83. Epub 2011 Aug 6. PMID:21875802^[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
↑ Miura T, Fukami TA, Hasegawa K, Ono N, Suda A, Shindo H, Yoon DO, Kim SJ, Na YJ, Aoki Y, Shimma N, Tsukuda T, Shiratori Y. Lead generation of heat shock protein 90 inhibitors by a combination of fragment-based approach, virtual screening, and structure-based drug design. Bioorg Med Chem Lett. 2011 Oct 1;21(19):5778-83. Epub 2011 Aug 6. PMID:21875802 doi:10.1016/j.bmcl.2011.08.001

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3b28"

Categories: Human | Large Structures | Fukami, T A | Ono, N | Chaperone-chaperone inhibitor complex

@@ Line 1: / Line 1: @@
 ==Hsp90 alpha N-terminal domain in complex with an inhibitor CH5015765==
-<StructureSection load='3b28' size='340' side='right' caption='[[3b28]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
+<StructureSection load='3b28' size='340' side='right'caption='[[3b28]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3b28]] 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=3B28 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3B28 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3b28]] 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=3B28 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3B28 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B2X:4-(5-CHLORO-1H,3H-BENZO[DE]ISOCHROMEN-6-YL)-6-(METHYLSULFANYL)-1,3,5-TRIAZIN-2-AMINE'>B2X</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B2X:4-(5-CHLORO-1H,3H-BENZO[DE]ISOCHROMEN-6-YL)-6-(METHYLSULFANYL)-1,3,5-TRIAZIN-2-AMINE'>B2X</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3b24|3b24]], [[3b25|3b25]], [[3b26|3b26]], [[3b27|3b27]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3b24|3b24]], [[3b25|3b25]], [[3b26|3b26]], [[3b27|3b27]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3b28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b28 OCA], [http://pdbe.org/3b28 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3b28 RCSB], [http://www.ebi.ac.uk/pdbsum/3b28 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3b28 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=3b28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b28 OCA], [https://pdbe.org/3b28 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3b28 RCSB], [https://www.ebi.ac.uk/pdbsum/3b28 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3b28 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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 22: @@
 ==See Also==
-*[[Heat Shock Proteins|Heat Shock Proteins]]
+*[[Heat Shock Protein structures|Heat Shock Protein structures]]
 == References ==
 <references/>
@@ Line 28: / Line 28: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Fukami, T A]]
 [[Category: Ono, N]]
 [[Category: Chaperone-chaperone inhibitor complex]]

3b28

From Proteopedia

Revision as of 11:21, 5 January 2022

Hsp90 alpha N-terminal domain in complex with an inhibitor CH5015765

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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