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''' | ==Structure and mechanism of a eukaryal nick-sealing RNA ligase== | ||
<StructureSection load='5cot' size='340' side='right' caption='[[5cot]], [[Resolution|resolution]] 1.69Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5cot]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5COT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5COT FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cou|5cou]], [[5cov|5cov]]</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=5cot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cot OCA], [http://pdbe.org/5cot PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cot RCSB], [http://www.ebi.ac.uk/pdbsum/5cot PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
ATP-dependent RNA ligases are agents of RNA repair that join 3'-OH and 5'-PO4 RNA ends. Naegleria gruberi RNA ligase (NgrRnl) exemplifies a family of RNA nick-sealing enzymes found in bacteria, viruses, and eukarya. Crystal structures of NgrRnl at three discrete steps along the reaction pathway-covalent ligase-(lysyl-Nzeta)-AMP*Mn(2+) intermediate; ligase*ATP*(Mn(2+))2 Michaelis complex; and ligase*Mn(2+) complex-highlight a two-metal mechanism of nucleotidyl transfer, whereby (i) an enzyme-bound "catalytic" metal coordination complex lowers the pKa of the lysine nucleophile and stabilizes the transition state of the ATP alpha phosphate; and (ii) a second metal coordination complex bridges the beta- and gamma-phosphates. The NgrRnl N domain is a distinctively embellished oligonucleotide-binding (OB) fold that engages the gamma-phosphate and associated metal complex and orients the pyrophosphate leaving group for in-line catalysis with stereochemical inversion at the AMP phosphate. The unique domain architecture of NgrRnl fortifies the theme that RNA ligases have evolved many times, and independently, by fusions of a shared nucleotidyltransferase domain to structurally diverse flanking modules. The mechanistic insights to lysine adenylylation gained from the NgrRnl structures are likely to apply broadly to the covalent nucleotidyltransferase superfamily of RNA ligases, DNA ligases, and RNA capping enzymes. | |||
Structure and two-metal mechanism of a eukaryal nick-sealing RNA ligase.,Unciuleac MC, Goldgur Y, Shuman S Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):13868-73. doi:, 10.1073/pnas.1516536112. Epub 2015 Oct 28. PMID:26512110<ref>PMID:26512110</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5cot" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Goldgur, Y]] | [[Category: Goldgur, Y]] | ||
[[Category: Shuman, S]] | [[Category: Shuman, S]] | ||
[[Category: Unciuleac, M C]] | |||
[[Category: Adenylyltransferase]] | |||
[[Category: Ligase]] | |||
[[Category: Rna repair]] | |||
Revision as of 00:30, 1 December 2015
Structure and mechanism of a eukaryal nick-sealing RNA ligaseStructure and mechanism of a eukaryal nick-sealing RNA ligase
Structural highlights
Publication Abstract from PubMedATP-dependent RNA ligases are agents of RNA repair that join 3'-OH and 5'-PO4 RNA ends. Naegleria gruberi RNA ligase (NgrRnl) exemplifies a family of RNA nick-sealing enzymes found in bacteria, viruses, and eukarya. Crystal structures of NgrRnl at three discrete steps along the reaction pathway-covalent ligase-(lysyl-Nzeta)-AMP*Mn(2+) intermediate; ligase*ATP*(Mn(2+))2 Michaelis complex; and ligase*Mn(2+) complex-highlight a two-metal mechanism of nucleotidyl transfer, whereby (i) an enzyme-bound "catalytic" metal coordination complex lowers the pKa of the lysine nucleophile and stabilizes the transition state of the ATP alpha phosphate; and (ii) a second metal coordination complex bridges the beta- and gamma-phosphates. The NgrRnl N domain is a distinctively embellished oligonucleotide-binding (OB) fold that engages the gamma-phosphate and associated metal complex and orients the pyrophosphate leaving group for in-line catalysis with stereochemical inversion at the AMP phosphate. The unique domain architecture of NgrRnl fortifies the theme that RNA ligases have evolved many times, and independently, by fusions of a shared nucleotidyltransferase domain to structurally diverse flanking modules. The mechanistic insights to lysine adenylylation gained from the NgrRnl structures are likely to apply broadly to the covalent nucleotidyltransferase superfamily of RNA ligases, DNA ligases, and RNA capping enzymes. Structure and two-metal mechanism of a eukaryal nick-sealing RNA ligase.,Unciuleac MC, Goldgur Y, Shuman S Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):13868-73. doi:, 10.1073/pnas.1516536112. Epub 2015 Oct 28. PMID:26512110[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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