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| | ==Crystal structure of tRNA wybutosine synthesizing enzyme TYW4== | | ==Crystal structure of tRNA wybutosine synthesizing enzyme TYW4== |
| - | <StructureSection load='2zzk' size='340' side='right' caption='[[2zzk]], [[Resolution|resolution]] 2.71Å' scene=''> | + | <StructureSection load='2zzk' size='340' side='right'caption='[[2zzk]], [[Resolution|resolution]] 2.71Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2zzk]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZZK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZZK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2zzk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZZK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zwa|2zwa]], [[2zw9|2zw9]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2zwa|2zwa]], [[2zw9|2zw9]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPM2, TYW4, YOL141W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPM2, TYW4, YOL141W ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</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=2zzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zzk OCA], [http://pdbe.org/2zzk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zzk RCSB], [http://www.ebi.ac.uk/pdbsum/2zzk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zzk ProSAT]</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=2zzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zzk OCA], [https://pdbe.org/2zzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zzk RCSB], [https://www.ebi.ac.uk/pdbsum/2zzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zzk ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TYW4_YEAST TYW4_YEAST]] S-adenosyl-L-methionine-dependent methyltransferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. Catalyzes the final 2 independent reactions, methylation of the alpha-carboxy group of wybutosine-72 to form wybutosine-58, and methoxycarbonylation of alpha-amino group of wybutosine-58 through the fixation of CO(2) to complete wybutosine.<ref>PMID:16642040</ref> <ref>PMID:17150819</ref> <ref>PMID:19287006</ref> | + | [[https://www.uniprot.org/uniprot/TYW4_YEAST TYW4_YEAST]] S-adenosyl-L-methionine-dependent methyltransferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. Catalyzes the final 2 independent reactions, methylation of the alpha-carboxy group of wybutosine-72 to form wybutosine-58, and methoxycarbonylation of alpha-amino group of wybutosine-58 through the fixation of CO(2) to complete wybutosine.<ref>PMID:16642040</ref> <ref>PMID:17150819</ref> <ref>PMID:19287006</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Atcc 18824]] | | [[Category: Atcc 18824]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Ishitani, R]] | | [[Category: Ishitani, R]] |
| | [[Category: Noma, A]] | | [[Category: Noma, A]] |
| Structural highlights
Function
[TYW4_YEAST] S-adenosyl-L-methionine-dependent methyltransferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. Catalyzes the final 2 independent reactions, methylation of the alpha-carboxy group of wybutosine-72 to form wybutosine-58, and methoxycarbonylation of alpha-amino group of wybutosine-58 through the fixation of CO(2) to complete wybutosine.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Wybutosine (yW), one of the most complicated modified nucleosides, is found in the anticodon loop of eukaryotic phenylalanine tRNA. This hypermodified nucleoside ensures correct codon recognition by stabilizing codon-anticodon pairings during the decoding process in the ribosome. TYW4 is an S-adenosylmethionine (SAM)-dependent enzyme that catalyzes the final step of yW biosynthesis, methylation and methoxycarbonylation. However, the structural basis for the catalytic mechanism by TYW4, and especially that for the methoxycarbonylation, have remained elusive. Here we report the apo and cofactor-bound crystal structures of yeast TYW4. The structures revealed that the C-terminal domain folds into a beta-propeller structure, forming part of the binding pocket for the target nucleoside. A comparison of the apo, SAM-bound, and S-adenosylhomocysteine-bound structures of TYW4 revealed a drastic structural change upon cofactor binding, which may sequester solvent from the catalytic site during the reaction and facilitate product release after the reaction. In conjunction with the functional analysis, our results suggest that TYW4 catalyzes both methylation and methoxycarbonylation at a single catalytic site, and in the latter reaction, the methoxycarbonyl group is formed through the fixation of carbon dioxide.
Structural basis of tRNA modification with CO2 fixation and methylation by wybutosine synthesizing enzyme TYW4.,Suzuki Y, Noma A, Suzuki T, Ishitani R, Nureki O Nucleic Acids Res. 2009 May;37(9):2910-25. Epub 2009 Mar 14. PMID:19287006[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Noma A, Kirino Y, Ikeuchi Y, Suzuki T. Biosynthesis of wybutosine, a hyper-modified nucleoside in eukaryotic phenylalanine tRNA. EMBO J. 2006 May 17;25(10):2142-54. Epub 2006 Apr 27. PMID:16642040 doi:http://dx.doi.org/7601105
- ↑ Noma A, Suzuki T. Ribonucleome analysis identified enzyme genes responsible for wybutosine synthesis. Nucleic Acids Symp Ser (Oxf). 2006;(50):65-6. PMID:17150819 doi:http://dx.doi.org/10.1093/nass/nrl032
- ↑ Suzuki Y, Noma A, Suzuki T, Ishitani R, Nureki O. Structural basis of tRNA modification with CO2 fixation and methylation by wybutosine synthesizing enzyme TYW4. Nucleic Acids Res. 2009 May;37(9):2910-25. Epub 2009 Mar 14. PMID:19287006 doi:10.1093/nar/gkp158
- ↑ Suzuki Y, Noma A, Suzuki T, Ishitani R, Nureki O. Structural basis of tRNA modification with CO2 fixation and methylation by wybutosine synthesizing enzyme TYW4. Nucleic Acids Res. 2009 May;37(9):2910-25. Epub 2009 Mar 14. PMID:19287006 doi:10.1093/nar/gkp158
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