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| | <StructureSection load='5u32' size='340' side='right'caption='[[5u32]], [[Resolution|resolution]] 2.19Å' scene=''> | | <StructureSection load='5u32' size='340' side='right'caption='[[5u32]], [[Resolution|resolution]] 2.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5u32]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Canal Canal]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U32 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U32 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5u32]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_albicans_SC5314 Candida albicans SC5314]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U32 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U32 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.191Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LIG1, RLG1, TRL1, CAALFM_C702060WA, CaJ7.0238, CaO19.13864, CaO19.6511 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=237561 CANAL])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA_ligase_(ATP) RNA ligase (ATP)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.5.1.3 6.5.1.3] </span></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=5u32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u32 OCA], [https://pdbe.org/5u32 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u32 RCSB], [https://www.ebi.ac.uk/pdbsum/5u32 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u32 ProSAT]</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=5u32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u32 OCA], [http://pdbe.org/5u32 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u32 RCSB], [http://www.ebi.ac.uk/pdbsum/5u32 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u32 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/TRNL_CANAL TRNL_CANAL] One of the two proteins required for the splicing of precursor tRNA molecules containing introns. The ligation activity requires three enzymatic activities: phosphorylation of the 5' terminus of the 3' half-tRNA in the presence of ATP, opening of the 2'3'-cyclic phosphodiester bond of the 5' half-tRNA leaving a 2'-phosphomonoester and ligation of the two tRNA halves in an ATP-dependent reaction. |
| - | Fungal tRNA ligase (Trl1) is an essential enzyme that repairs RNA breaks with 2',3'-cyclic-PO4 and 5'-OH ends inflicted during tRNA splicing and non-canonical mRNA splicing in the fungal unfolded protein response. Trl1 is composed of C-terminal cyclic phosphodiesterase and central polynucleotide kinase domains that heal the broken ends to generate the 3'-OH,2'-PO4 and 5'-PO4 termini required for sealing by an N-terminal ligase domain. Trl1 enzymes are found in all human fungal pathogens and are promising targets for antifungal drug discovery because their domain compositions and biochemical mechanisms are unique compared to the mammalian RtcB-type tRNA splicing enzyme. A distinctive feature of Trl1 is its preferential use of GTP as phosphate donor for the RNA kinase reaction. Here we report the 2.2 A crystal structure of the kinase domain of Trl1 from the fungal pathogen Candida albicans with GDP and Mg2+ in the active site. The P-loop phosphotransferase fold of the kinase is embellished by a unique 'G-loop' element that accounts for guanine nucleotide specificity. Mutations of amino acids that contact the guanine nucleobase efface kinase activity in vitro and Trl1 function in vivo. Our findings fortify the case for the Trl1 kinase as an antifungal target.
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| - | Structural basis for the GTP specificity of the RNA kinase domain of fungal tRNA ligase.,Remus BS, Goldgur Y, Shuman S Nucleic Acids Res. 2017 Nov 20. pii: 4641907. doi: 10.1093/nar/gkx1159. PMID:29165709<ref>PMID:29165709</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 5u32" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Canal]] | + | [[Category: Candida albicans SC5314]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Goldgur, Y]] | + | [[Category: Goldgur Y]] |
| - | [[Category: Remus, B S]] | + | [[Category: Remus BS]] |
| - | [[Category: Shuman, S]] | + | [[Category: Shuman S]] |
| - | [[Category: Polynucleotide kinase]]
| + | |
| - | [[Category: Rna ligase]]
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| - | [[Category: Rna repair]]
| + | |
| - | [[Category: Transferase]]
| + | |
