This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


6d36

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: '''Unreleased structure''' The entry 6d36 is ON HOLD Authors: Description: Category: Unreleased Structures)
Current revision (15:17, 4 October 2023) (edit) (undo)
 
(3 intermediate revisions not shown.)
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 6d36 is ON HOLD
+
==Structure of human ARH3 bound to ADP-ribose and magnesium==
 +
<StructureSection load='6d36' size='340' side='right'caption='[[6d36]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[6d36]] 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=6D36 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D36 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]] 1.7&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=6d36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d36 OCA], [https://pdbe.org/6d36 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d36 RCSB], [https://www.ebi.ac.uk/pdbsum/6d36 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d36 ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/ADPRS_HUMAN ADPRS_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/ADPRS_HUMAN ADPRS_HUMAN] ADP-ribose glycohydrolase that preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on serine, free poly(ADP-ribose) and O-acetyl-ADP-D-ribose (PubMed:21498885, PubMed:30045870, PubMed:29907568, PubMed:30401461, PubMed:33186521). Specifically acts as a serine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to serine residues on proteins, thereby playing a key role in DNA damage response (PubMed:28650317, PubMed:29234005, PubMed:30045870, PubMed:33186521). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802, PubMed:33186521). Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds (PubMed:16278211). Also able to degrade protein free poly(ADP-ribose), which is synthesized in response to DNA damage: free poly(ADP-ribose) acts as a potent cell death signal and its degradation by ADPRHL2 protects cells from poly(ADP-ribose)-dependent cell death, a process named parthanatos (PubMed:16278211). Also hydrolyzes free poly(ADP-ribose) in mitochondria (PubMed:22433848). Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins (PubMed:17075046, PubMed:21498885). Specifically degrades 1''-O-acetyl-ADP-D-ribose isomer, rather than 2''-O-acetyl-ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose isomers (PubMed:21498885).<ref>PMID:16278211</ref> <ref>PMID:17075046</ref> <ref>PMID:21498885</ref> <ref>PMID:22433848</ref> <ref>PMID:28650317</ref> <ref>PMID:29234005</ref> <ref>PMID:29480802</ref> <ref>PMID:29907568</ref> <ref>PMID:30045870</ref> <ref>PMID:30401461</ref> <ref>PMID:33186521</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
ADP-ribosyl-acceptor hydrolase 3 (ARH3) plays important roles in regulation of poly(ADP-ribosyl)ation, a reversible post-translational modification, and in maintenance of genomic integrity. ARH3 degrades poly(ADP-ribose) to protect cells from poly(ADP-ribose)-dependent cell death, reverses serine mono(ADP-ribosyl)ation, and hydrolyzes O-acetyl-ADP-ribose, a product of Sirtuin-catalyzed histone deacetylation. ARH3 preferentially hydrolyzes O-linkages attached to the anomeric C1'' of ADP-ribose; however, how ARH3 specifically recognizes and cleaves structurally diverse substrates remains unknown. Here, structures of full-length human ARH3 bound to ADP-ribose and Mg(2+), coupled with computational modeling, reveal a dramatic conformational switch from closed to open states that enables specific substrate recognition. The glutamate flap, which blocks substrate entrance to Mg(2+) in the unliganded closed state, is ejected from the active site when substrate is bound. This closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2''- and 3''-hydroxyls of ADP-ribose. Our collective data uncover an unprecedented structural plasticity of ARH3 that supports its specificity for the 1''-O-linkage in substrates and Mg(2+)-dependent catalysis.
-
Authors:
+
Structure of human ADP-ribosyl-acceptor hydrolase 3 bound to ADP-ribose reveals a conformational switch that enables specific substrate recognition.,Pourfarjam Y, Ventura J, Kurinov I, Cho A, Moss J, Kim IK J Biol Chem. 2018 Aug 10;293(32):12350-12359. doi: 10.1074/jbc.RA118.003586. Epub, 2018 Jun 15. PMID:29907568<ref>PMID:29907568</ref>
-
Description:
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
 +
<div class="pdbe-citations 6d36" style="background-color:#fffaf0;"></div>
 +
 
 +
==See Also==
 +
*[[Poly(ADP-ribose) glycohydrolase 3D structures|Poly(ADP-ribose) glycohydrolase 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Homo sapiens]]
 +
[[Category: Large Structures]]
 +
[[Category: Kim IK]]
 +
[[Category: Kurinov I]]
 +
[[Category: Pourfarjam Y]]
 +
[[Category: Ventura J]]

Current revision

Structure of human ARH3 bound to ADP-ribose and magnesium

PDB ID 6d36

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6d36"
Personal tools