6bhv
From Proteopedia
(Difference between revisions)
| (3 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
==Human PARP-1 bound to NAD+ analog benzamide adenine dinucleotide (BAD)== | ==Human PARP-1 bound to NAD+ analog benzamide adenine dinucleotide (BAD)== | ||
| - | <StructureSection load='6bhv' size='340' side='right' caption='[[6bhv]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='6bhv' size='340' side='right'caption='[[6bhv]], [[Resolution|resolution]] 2.30Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6bhv]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BHV OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6bhv]] is a 4 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=6BHV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BHV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DQV:[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl+[(2R,3S,4R,5S)-5-(3-carbamoylphenyl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl+dihydrogen+diphosphate+(non-preferred+name)'>DQV</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DQV:[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl+[(2R,3S,4R,5S)-5-(3-carbamoylphenyl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl+dihydrogen+diphosphate+(non-preferred+name)'>DQV</scene></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6bhv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bhv OCA], [https://pdbe.org/6bhv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bhv RCSB], [https://www.ebi.ac.uk/pdbsum/6bhv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bhv ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/PARP1_HUMAN PARP1_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. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.<ref>PMID:17177976</ref> <ref>PMID:18172500</ref> <ref>PMID:19344625</ref> <ref>PMID:19661379</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | PARP-1 cleaves NAD(+) and transfers the resulting ADP-ribose moiety onto target proteins and onto subsequent polymers of ADP-ribose. An allosteric network connects PARP-1 multi-domain detection of DNA damage to catalytic domain structural changes that relieve catalytic autoinhibition; however, the mechanism of autoinhibition is undefined. Here, we show using the non-hydrolyzable NAD(+) analog benzamide adenine dinucleotide (BAD) that PARP-1 autoinhibition results from a selective block on NAD(+) binding. Following DNA damage detection, BAD binding to the catalytic domain leads to changes in PARP-1 dynamics at distant DNA-binding surfaces, resulting in increased affinity for DNA damage, and providing direct evidence of reverse allostery. Our findings reveal a two-step mechanism to activate and to then stabilize PARP-1 on a DNA break, indicate that PARP-1 allostery influences persistence on DNA damage, and have important implications for PARP inhibitors that engage the NAD(+) binding site. | ||
| + | |||
| + | NAD(+) analog reveals PARP-1 substrate-blocking mechanism and allosteric communication from catalytic center to DNA-binding domains.,Langelier MF, Zandarashvili L, Aguiar PM, Black BE, Pascal JM Nat Commun. 2018 Feb 27;9(1):844. doi: 10.1038/s41467-018-03234-8. PMID:29487285<ref>PMID:29487285</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6bhv" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Langelier MF]] |
| - | [[Category: | + | [[Category: Pascal JM]] |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
Human PARP-1 bound to NAD+ analog benzamide adenine dinucleotide (BAD)
| |||||||||||
