2p2c: Difference between revisions

From Proteopedia
Jump to navigationJump to search
OCA (talk | contribs)
No edit summary
OCA (talk | contribs)
No edit summary
 
(12 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2p2c.gif|left|200px]]
<!--
The line below this paragraph, containing "STRUCTURE_2p2c", creates the "Structure Box" on the page.
You may change the PDB parameter (which sets the PDB file loaded into the applet)
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
or leave the SCENE parameter empty for the default display.
-->
{{STRUCTURE_2p2c|  PDB=2p2c  |  SCENE=  }}
'''Inhibition of caspase-2 by a designed ankyrin repeat protein (DARPin)'''


==Inhibition of caspase-2 by a designed ankyrin repeat protein (DARPin)==
<StructureSection load='2p2c' size='340' side='right'caption='[[2p2c]], [[Resolution|resolution]] 3.24&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2p2c]] is a 18 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=2P2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P2C FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.24&#8491;</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=2p2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p2c OCA], [https://pdbe.org/2p2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p2c RCSB], [https://www.ebi.ac.uk/pdbsum/2p2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p2c ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CASP2_HUMAN CASP2_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival.
== 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/p2/2p2c_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=2p2c ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Specific and potent caspase inhibitors are indispensable for the dissection of the intricate pathways leading to apoptosis. We selected a designed ankyrin repeat protein (DARPin) from a combinatorial library that inhibits caspase-2 in vitro with a subnanomolar inhibition constant and, in contrast to the peptidic caspase inhibitors, with very high specificity for this particular caspase. The crystal structure of this inhibitor (AR_F8) in complex with caspase-2 reveals the molecular basis for the specificity and, together with kinetic analyses, the allosteric mechanism of inhibition. The structure also shows a conformation of the active site that can be exploited for the design of inhibitory compounds. AR_F8 is a specific inhibitor of an initiator caspase and has the potential to help identify the function of caspase-2 in the complex biological apoptotic signaling network.


==Overview==
Inhibition of caspase-2 by a designed ankyrin repeat protein: specificity, structure, and inhibition mechanism.,Schweizer A, Roschitzki-Voser H, Amstutz P, Briand C, Gulotti-Georgieva M, Prenosil E, Binz HK, Capitani G, Baici A, Pluckthun A, Grutter MG Structure. 2007 May;15(5):625-36. PMID:17502107<ref>PMID:17502107</ref>
Specific and potent caspase inhibitors are indispensable for the dissection of the intricate pathways leading to apoptosis. We selected a designed ankyrin repeat protein (DARPin) from a combinatorial library that inhibits caspase-2 in vitro with a subnanomolar inhibition constant and, in contrast to the peptidic caspase inhibitors, with very high specificity for this particular caspase. The crystal structure of this inhibitor (AR_F8) in complex with caspase-2 reveals the molecular basis for the specificity and, together with kinetic analyses, the allosteric mechanism of inhibition. The structure also shows a conformation of the active site that can be exploited for the design of inhibitory compounds. AR_F8 is a specific inhibitor of an initiator caspase and has the potential to help identify the function of caspase-2 in the complex biological apoptotic signaling network.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2P2C is a [[Protein complex]] structure of sequences 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=2P2C OCA].
</div>
<div class="pdbe-citations 2p2c" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Inhibition of caspase-2 by a designed ankyrin repeat protein: specificity, structure, and inhibition mechanism., Schweizer A, Roschitzki-Voser H, Amstutz P, Briand C, Gulotti-Georgieva M, Prenosil E, Binz HK, Capitani G, Baici A, Pluckthun A, Grutter MG, Structure. 2007 May;15(5):625-36. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17502107 17502107]
*[[Caspase 3D structures|Caspase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Briand, C.]]
[[Category: Briand C]]
[[Category: Capitani, G.]]
[[Category: Capitani G]]
[[Category: Gruetter, M G.]]
[[Category: Gruetter MG]]
[[Category: Voser, HRoschitzki.]]
[[Category: Roschitzki Voser H]]
[[Category: Apoptosis]]
[[Category: Caspase]]
[[Category: Caspase-2]]
[[Category: Designed ankyrin repeat protein]]
[[Category: Inhibition]]
[[Category: Protein design]]
[[Category: Protein library]]
[[Category: Ribosome display]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 12:11:39 2008''

Latest revision as of 05:25, 17 October 2024

Inhibition of caspase-2 by a designed ankyrin repeat protein (DARPin)

2p2c, resolution 3.24Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA