3mnr

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of Benzamide SNX-1321 bound to Hsp90

Structural highlights

3mnr is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
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

A chemoproteomics-based drug discovery strategy is presented that utilizes a highly parallel screening platform, encompassing more than 1000 targets, with a focused chemical library prior to target selection. This chemoproteomics-based process enables a data-driven selection of both the biological target and chemical hit after the screen is complete. The methodology has been exemplified for the purine binding proteome (proteins utilizing ATP, NAD, FAD). Screening of an 8000 member library yielded over 1500 unique protein-ligand interactions, which included novel hits for the oncology target Hsp90. The approach, which also provides broad target selectivity information, was used to drive the identification of a potent and orally active Hsp90 inhibitor, SNX-5422, which is currently in phase 1 clinical studies.

Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90.,Fadden P, Huang KH, Veal JM, Steed PM, Barabasz AF, Foley B, Hu M, Partridge JM, Rice J, Scott A, Dubois LG, Freed TA, Silinski MA, Barta TE, Hughes PF, Ommen A, Ma W, Smith ED, Spangenberg AW, Eaves J, Hanson GJ, Hinkley L, Jenks M, Lewis M, Otto J, Pronk GJ, Verleysen K, Haystead TA, Hall SE Chem Biol. 2010 Jul 30;17(7):686-94. PMID:20659681^[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
↑ Fadden P, Huang KH, Veal JM, Steed PM, Barabasz AF, Foley B, Hu M, Partridge JM, Rice J, Scott A, Dubois LG, Freed TA, Silinski MA, Barta TE, Hughes PF, Ommen A, Ma W, Smith ED, Spangenberg AW, Eaves J, Hanson GJ, Hinkley L, Jenks M, Lewis M, Otto J, Pronk GJ, Verleysen K, Haystead TA, Hall SE. Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90. Chem Biol. 2010 Jul 30;17(7):686-94. PMID:20659681 doi:10.1016/j.chembiol.2010.04.015

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/3mnr"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Benzamide SNX-1321 bound to Hsp90==
-<StructureSection load='3mnr' size='340' side='right' caption='[[3mnr]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='3mnr' size='340' side='right'caption='[[3mnr]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3mnr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MNR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MNR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3mnr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MNR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MNR FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SD1:2-[(3,4,5-TRIMETHOXYPHENYL)AMINO]-4-(2,6,6-TRIMETHYL-4-OXO-4,5,6,7-TETRAHYDRO-1H-INDOL-1-YL)BENZAMIDE'>SD1</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3d0b|3d0b]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SD1:2-[(3,4,5-TRIMETHOXYPHENYL)AMINO]-4-(2,6,6-TRIMETHYL-4-OXO-4,5,6,7-TETRAHYDRO-1H-INDOL-1-YL)BENZAMIDE'>SD1</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=3mnr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mnr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3mnr RCSB], [http://www.ebi.ac.uk/pdbsum/3mnr PDBsum]</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=3mnr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mnr OCA], [https://pdbe.org/3mnr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mnr RCSB], [https://www.ebi.ac.uk/pdbsum/3mnr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mnr ProSAT]</span></td></tr>
 </table>
+== Function ==
+[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mn/3mnr_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mn/3mnr_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3mnr ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 25: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3mnr" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Heat Shock Proteins|Heat Shock Proteins]]
+*[[Heat Shock Protein structures|Heat Shock Protein structures]]
 == References ==
 <references/>
@@ Line 33: / Line 37: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Fadden, P]]
+[[Category: Large Structures]]
-[[Category: Hall, S E]]
+[[Category: Fadden P]]
-[[Category: Haytstead, T A]]
+[[Category: Hall SE]]
-[[Category: Huang, K H]]
+[[Category: Haytstead TA]]
-[[Category: Rice, J]]
+[[Category: Huang KH]]
-[[Category: Veal, J M]]
+[[Category: Rice J]]
-[[Category: Chaperone]]
+[[Category: Veal JM]]
-[[Category: Heat shock protein 90]]
-[[Category: Hsp90]]
-[[Category: Protein-ligand complex]]

3mnr

From Proteopedia

Current revision

Crystal Structure of Benzamide SNX-1321 bound to Hsp90

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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