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1nme

From Proteopedia

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Structure of Casp-3 with tethered salicylate

Structural highlights

1nme is a 2 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 1.6Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CASP3_HUMAN Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.^[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

Cysteine aspartyl protease-3 (caspase-3) is a mediator of apoptosis and a therapeutic target for a wide range of diseases. Using a dynamic combinatorial technology, 'extended tethering', we identified unique nonpeptidic inhibitors for this enzyme. Extended tethering allowed the identification of ligands that bind to discrete regions of caspase-3 and also helped direct the assembly of these ligands into small-molecule inhibitors. We first designed a small-molecule 'extender' that irreversibly alkylates the cysteine residue of caspase-3 and also contains a thiol group. The modified protein was then screened against a library of disulfide-containing small-molecule fragments. Mass-spectrometry was used to identify ligands that bind noncovalently to the protein and that also form a disulfide linkage with the extender. Linking the selected fragments with binding elements from the extenders generates reversible, tight-binding molecules that are druglike and distinct from known inhibitors. One molecule derived from this approach inhibited apoptosis in cells.

In situ assembly of enzyme inhibitors using extended tethering.,Erlanson DA, Lam JW, Wiesmann C, Luong TN, Simmons RL, DeLano WL, Choong IC, Burdett MT, Flanagan WM, Lee D, Gordon EM, O'Brien T Nat Biotechnol. 2003 Mar;21(3):308-14. Epub 2003 Feb 3. PMID:12563278^[3]

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

References

↑ Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, et al.. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 1995 Jul 6;376(6535):37-43. PMID:7596430 doi:http://dx.doi.org/10.1038/376037a0
↑ Cabrera JR, Bouzas-Rodriguez J, Tauszig-Delamasure S, Mehlen P. RET modulates cell adhesion via its cleavage by caspase in sympathetic neurons. J Biol Chem. 2011 Apr 22;286(16):14628-38. doi: 10.1074/jbc.M110.195461. Epub, 2011 Feb 28. PMID:21357690 doi:10.1074/jbc.M110.195461
↑ Erlanson DA, Lam JW, Wiesmann C, Luong TN, Simmons RL, DeLano WL, Choong IC, Burdett MT, Flanagan WM, Lee D, Gordon EM, O'Brien T. In situ assembly of enzyme inhibitors using extended tethering. Nat Biotechnol. 2003 Mar;21(3):308-14. Epub 2003 Feb 3. PMID:12563278 doi:10.1038/nbt786

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/1nme"

@@ Line 1: / Line 1: @@
 ==Structure of Casp-3 with tethered salicylate==
-<StructureSection load='1nme' size='340' side='right' caption='[[1nme]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+<StructureSection load='1nme' size='340' side='right'caption='[[1nme]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1nme]] 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=1NME OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NME FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1nme]] is a 2 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=1NME OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NME FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=158:3-(2-MERCAPTO-ACETYLAMINO)-4-OXO-PENTANOIC+ACID'>158</scene>, <scene name='pdbligand=159:2-HYDROXY-5-(2-MERCAPTO-ETHYLSULFAMOYL)-BENZOIC+ACID'>159</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]] 1.6&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nmq|1nmq]], [[1nms|1nms]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=158:3-(2-MERCAPTO-ACETYLAMINO)-4-OXO-PENTANOIC+ACID'>158</scene>, <scene name='pdbligand=159:2-HYDROXY-5-(2-MERCAPTO-ETHYLSULFAMOYL)-BENZOIC+ACID'>159</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=1nme FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nme OCA], [http://pdbe.org/1nme PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1nme RCSB], [http://www.ebi.ac.uk/pdbsum/1nme PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1nme 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=1nme FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nme OCA], [https://pdbe.org/1nme PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nme RCSB], [https://www.ebi.ac.uk/pdbsum/1nme PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nme ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CASP3_HUMAN CASP3_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.<ref>PMID:7596430</ref> <ref>PMID:21357690</ref>
+[https://www.uniprot.org/uniprot/CASP3_HUMAN CASP3_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.<ref>PMID:7596430</ref> <ref>PMID:21357690</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/nm/1nme_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nm/1nme_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 29: / Line 29: @@
 </div>
 <div class="pdbe-citations 1nme" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Caspase 3D structures|Caspase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Brian, T O]]
+[[Category: Large Structures]]
-[[Category: Choong, I C]]
+[[Category: Choong IC]]
-[[Category: DeLano, W]]
+[[Category: DeLano W]]
-[[Category: Erlanson, D A]]
+[[Category: Erlanson DA]]
-[[Category: Flanagan, M]]
+[[Category: Flanagan M]]
-[[Category: Lam, J]]
+[[Category: Lam J]]
-[[Category: Lee, D]]
+[[Category: Lee D]]
-[[Category: Luong, T N]]
+[[Category: Luong TN]]
-[[Category: Simmons, B]]
+[[Category: O'Brian T]]
-[[Category: Wiesmann, C]]
+[[Category: Simmons B]]
-[[Category: Apoptosis]]
+[[Category: Wiesmann C]]
-[[Category: Cysteine proteinase]]
-[[Category: Hydrolase]]
-[[Category: Sulfonamide inhibition]]

1nme

From Proteopedia

Current revision

Structure of Casp-3 with tethered salicylate

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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