4q93

From Proteopedia

(Difference between revisions)

Revision as of 17:17, 4 January 2017

Crystal structure of resveratrol bound human tyrosyl tRNA synthetase

Structural highlights

4q93 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	1q11, 1n3l, 4qbt
Activity:	Tyrosine--tRNA ligase, with EC number 6.1.1.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SYYC_HUMAN] Defects in YARS are the cause of Charcot-Marie-Tooth disease dominant intermediate type C (CMTDIC) [MIM:608323]. CMTDIC is a form of Charcot-Marie-Tooth disease characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.^[1]

Function

[SYYC_HUMAN] Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr) (By similarity).

Publication Abstract from PubMed

Resveratrol is reported to extend lifespan and provide cardio-neuro-protective, anti-diabetic, and anti-cancer effects by initiating a stress response that induces survival genes. Because human tyrosyl transfer-RNA (tRNA) synthetase (TyrRS) translocates to the nucleus under stress conditions, we considered the possibility that the tyrosine-like phenolic ring of resveratrol might fit into the active site pocket to effect a nuclear role. Here we present a 2.1 A co-crystal structure of resveratrol bound to the active site of TyrRS. Resveratrol nullifies the catalytic activity and redirects TyrRS to a nuclear function, stimulating NAD+-dependent auto-poly-ADP-ribosylation of poly(ADP-ribose) polymerase 1 (PARP1). Downstream activation of key stress signalling pathways are causally connected to TyrRS-PARP1-NAD+ collaboration. This collaboration is also demonstrated in the mouse, and is specifically blocked in vivo by a resveratrol-displacing tyrosyl adenylate analogue. In contrast to functionally diverse tRNA synthetase catalytic nulls created by alternative splicing events that ablate active sites, here a non-spliced TyrRS catalytic null reveals a new PARP1- and NAD+-dependent dimension to the physiological mechanism of resveratrol.

A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol.,Sajish M, Schimmel P Nature. 2014 Dec 22. doi: 10.1038/nature14028. PMID:25533949^[2]

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

References

↑ Jordanova A, Irobi J, Thomas FP, Van Dijck P, Meerschaert K, Dewil M, Dierick I, Jacobs A, De Vriendt E, Guergueltcheva V, Rao CV, Tournev I, Gondim FA, D'Hooghe M, Van Gerwen V, Callaerts P, Van Den Bosch L, Timmermans JP, Robberecht W, Gettemans J, Thevelein JM, De Jonghe P, Kremensky I, Timmerman V. Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy. Nat Genet. 2006 Feb;38(2):197-202. Epub 2006 Jan 22. PMID:16429158 doi:10.1038/ng1727
↑ Sajish M, Schimmel P. A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. Nature. 2014 Dec 22. doi: 10.1038/nature14028. PMID:25533949 doi:http://dx.doi.org/10.1038/nature14028

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4q93"

@@ Line 1: / Line 1: @@
 ==Crystal structure of resveratrol bound human tyrosyl tRNA synthetase==
 <StructureSection load='4q93' size='340' side='right' caption='[[4q93]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1q11|1q11]], [[1n3l|1n3l]], [[4qbt|4qbt]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tyrosine--tRNA_ligase Tyrosine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.1 6.1.1.1] </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=4q93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q93 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q93 RCSB], [http://www.ebi.ac.uk/pdbsum/4q93 PDBsum]</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=4q93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q93 OCA], [http://pdbe.org/4q93 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4q93 RCSB], [http://www.ebi.ac.uk/pdbsum/4q93 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4q93 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4q93" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4q93

From Proteopedia

Revision as of 17:17, 4 January 2017

Crystal structure of resveratrol bound human tyrosyl tRNA synthetase

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox