4xit: Difference between revisions

Revision as of 07:06, 29 May 2019

Discovery of novel oxazepine and diazepine carboxamides as two new classes of heat shock protein 90 inhibitors

Structural highlights

4xit 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:	40Z, GOL
Related:	4xip, 4xir, 4xiq
Gene:	HSP90AA1, HSP90A, HSPC1, HSPCA (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

Two novel series of oxazepine and diazepine based HSP90 inhibitors are reported. This effort relied on structure based design and isothermal calorimetry to identify small drug like macrocycles. Computational modelling was used to build into a solvent exposed pocket near the opening of the ATP binding site, which led to potent inhibitors of HSP90 (25-30).

Discovery of novel oxazepine and diazepine carboxamides as two new classes of heat shock protein 90 inhibitors.,Neubert T, Numa M, Ernst J, Clemens J, Krenitsky P, Liu M, Fleck B, Woody L, Zuccola H, Stamos D Bioorg Med Chem Lett. 2015 Mar 15;25(6):1338-42. doi: 10.1016/j.bmcl.2015.01.023., Epub 2015 Jan 20. PMID:25677667^[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
↑ Neubert T, Numa M, Ernst J, Clemens J, Krenitsky P, Liu M, Fleck B, Woody L, Zuccola H, Stamos D. Discovery of novel oxazepine and diazepine carboxamides as two new classes of heat shock protein 90 inhibitors. Bioorg Med Chem Lett. 2015 Mar 15;25(6):1338-42. doi: 10.1016/j.bmcl.2015.01.023., Epub 2015 Jan 20. PMID:25677667 doi:https://dx.doi.org/10.1016/j.bmcl.2015.01.023

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] Neubert T, Numa M, Ernst J, Clemens J, Krenitsky P, Liu M, Fleck B, Woody L, Zuccola H, Stamos D. Discovery of novel oxazepine and diazepine carboxamides as two new classes of heat shock protein 90 inhibitors. Bioorg Med Chem Lett. 2015 Mar 15;25(6):1338-42. doi: 10.1016/j.bmcl.2015.01.023., Epub 2015 Jan 20. PMID:25677667 doi:https://dx.doi.org/10.1016/j.bmcl.2015.01.023

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
 ==Discovery of novel oxazepine and diazepine carboxamides as two new classes of heat shock protein 90 inhibitors==
-<StructureSection load='4xit' size='340' side='right' caption='[[4xit]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
+<StructureSection load='4xit' size='340' side='right'caption='[[4xit]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4xit]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XIT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XIT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4xit]] 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=4XIT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XIT FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=40Z:2-CHLORO-5-(FURAN-2-YLMETHYL)-8,11,11-TRIMETHYL-9-OXO-6,7,9,10,11,12-HEXAHYDRO-5H-INDOLO[1,2-A][1,5]BENZODIAZEPINE-3-CARBOXAMIDE'>40Z</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xip|4xip]], [[4xir|4xir]], [[4xiq|4xiq]]</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=4xit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xit OCA], [http://pdbe.org/4xit PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xit RCSB], [http://www.ebi.ac.uk/pdbsum/4xit PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, HSPC1, HSPCA ([http://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=4xit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xit OCA], [http://pdbe.org/4xit PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xit RCSB], [http://www.ebi.ac.uk/pdbsum/4xit PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xit ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 26: / Line 27: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Neubert, T]]
 [[Category: Zuccola, H J]]
 [[Category: Chaperone-chaperone inhibitor complex]]

4xit: Difference between revisions

Revision as of 07:06, 29 May 2019

Discovery of novel oxazepine and diazepine carboxamides as two new classes of heat shock protein 90 inhibitors

Structural highlights

Function

Publication Abstract from PubMed

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References

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