5dsy: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 5dsy is ~~ON HOLD until Paper~~ Publication

==Crystal structure of constitutively active PARP-2==

== Structural highlights ==

<table><tr><td colspan='2'>[[5dsy]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DSY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DSY FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UHB:2-[4-[(2S,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]CARBONYLPIPERAZIN-1-YL]-N-(1-OXIDANYLIDENE-2,3-DIHYDROISOINDOL-4-YL)ETHANAMIDE'>UHB</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></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=5dsy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dsy OCA], [http://pdbe.org/5dsy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dsy RCSB], [http://www.ebi.ac.uk/pdbsum/5dsy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dsy ProSAT]</span></td></tr>

</table>

== Function ==

[[http://www.uniprot.org/uniprot/PARP2_HUMAN PARP2_HUMAN]] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks.

== Publication Abstract from PubMed ==

Poly(ADP-ribose) polymerase-1 (PARP-1) creates the posttranslational modification PAR from substrate NAD(+) to regulate multiple cellular processes. DNA breaks sharply elevate PARP-1 catalytic activity to mount a cell survival repair response, whereas persistent PARP-1 hyperactivation during severe genotoxic stress is associated with cell death. The mechanism for tight control of the robust catalytic potential of PARP-1 remains unclear. By monitoring PARP-1 dynamics using hydrogen/deuterium exchange-mass spectrometry (HXMS), we unexpectedly find that a specific portion of the helical subdomain (HD) of the catalytic domain rapidly unfolds when PARP-1 encounters a DNA break. Together with biochemical and crystallographic analysis of HD deletion mutants, we show that the HD is an autoinhibitory domain that blocks productive NAD(+) binding. Our molecular model explains how PARP-1 DNA damage detection leads to local unfolding of the HD that relieves autoinhibition, and has important implications for the design of PARP inhibitors.

~~Authors:~~ Riccio, A.A., ~~Pascal, J.M~~.

PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain.,Dawicki-McKenna JM, Langelier MF, DeNizio JE, Riccio AA, Cao CD, Karch KR, McCauley M, Steffen JD, Black BE, Pascal JM Mol Cell. 2015 Dec 3;60(5):755-68. doi: 10.1016/j.molcel.2015.10.013. Epub 2015, Nov 25. PMID:26626480<ref>PMID:26626480</ref>

~~Description: Crystal structure~~ of ~~constitutively active PARP~~-2

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

[[Category: ~~Unreleased Structures~~]]

</div>

[[Category: Riccio, A.A]]

[[Category: ~~Pascal, J.M~~]]

== References ==

__TOC__

</StructureSection>

[[Category: Pascal, J M]]

[[Category: Riccio, A A]]

[[Category: Adp-ribosyl transferase]]

[[Category: Parp]]

[[Category: Parp-2]]

[[Category: Transferase]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5dsy is ON HOLD  until Paper Publication
+==Crystal structure of constitutively active PARP-2==
+<StructureSection load='5dsy' size='340' side='right' caption='[[5dsy]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5dsy]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DSY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DSY FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UHB:2-[4-[(2S,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]CARBONYLPIPERAZIN-1-YL]-N-(1-OXIDANYLIDENE-2,3-DIHYDROISOINDOL-4-YL)ETHANAMIDE'>UHB</scene></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></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=5dsy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dsy OCA], [http://pdbe.org/5dsy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dsy RCSB], [http://www.ebi.ac.uk/pdbsum/5dsy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dsy ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/PARP2_HUMAN PARP2_HUMAN]] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Poly(ADP-ribose) polymerase-1 (PARP-1) creates the posttranslational modification PAR from substrate NAD(+) to regulate multiple cellular processes. DNA breaks sharply elevate PARP-1 catalytic activity to mount a cell survival repair response, whereas persistent PARP-1 hyperactivation during severe genotoxic stress is associated with cell death. The mechanism for tight control of the robust catalytic potential of PARP-1 remains unclear. By monitoring PARP-1 dynamics using hydrogen/deuterium exchange-mass spectrometry (HXMS), we unexpectedly find that a specific portion of the helical subdomain (HD) of the catalytic domain rapidly unfolds when PARP-1 encounters a DNA break. Together with biochemical and crystallographic analysis of HD deletion mutants, we show that the HD is an autoinhibitory domain that blocks productive NAD(+) binding. Our molecular model explains how PARP-1 DNA damage detection leads to local unfolding of the HD that relieves autoinhibition, and has important implications for the design of PARP inhibitors.
-Authors: Riccio, A.A., Pascal, J.M.
+PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain.,Dawicki-McKenna JM, Langelier MF, DeNizio JE, Riccio AA, Cao CD, Karch KR, McCauley M, Steffen JD, Black BE, Pascal JM Mol Cell. 2015 Dec 3;60(5):755-68. doi: 10.1016/j.molcel.2015.10.013. Epub 2015, Nov 25. PMID:26626480<ref>PMID:26626480</ref>
-Description: Crystal structure of constitutively active PARP-2
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Riccio, A.A]]
+<div class="pdbe-citations 5dsy" style="background-color:#fffaf0;"></div>
-[[Category: Pascal, J.M]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Pascal, J M]]
+[[Category: Riccio, A A]]
+[[Category: Adp-ribosyl transferase]]
+[[Category: Parp]]
+[[Category: Parp-2]]
+[[Category: Transferase]]