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| | ==Structure of the E. coli Threonylcarbamoyl-AMP Synthase TSAC== | | ==Structure of the E. coli Threonylcarbamoyl-AMP Synthase TSAC== |
| - | <StructureSection load='2mx1' size='340' side='right'caption='[[2mx1]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mx1' size='340' side='right'caption='[[2mx1]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mx1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Ecoli Ecoli]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MX1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MX1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mx1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MX1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MX1 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b3282, JW3243, rimN, tsaC, yrdC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | </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=2mx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mx1 OCA], [https://pdbe.org/2mx1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mx1 RCSB], [https://www.ebi.ac.uk/pdbsum/2mx1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mx1 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/L-threonylcarbamoyladenylate_synthase L-threonylcarbamoyladenylate synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.87 2.7.7.87] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2mx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mx1 OCA], [https://pdbe.org/2mx1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mx1 RCSB], [https://www.ebi.ac.uk/pdbsum/2mx1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mx1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TSAC_ECOLI TSAC_ECOLI]] Required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. Catalyzes the conversion of L-threonine, bicarbonate/CO(2) and ATP to give threonylcarbamoyl-AMP (TC-AMP) as the acyladenylate intermediate, with the release of pyrophosphate. Is also able to catalyze the reverse reaction in vitro, i.e. the formation of ATP from TC-AMP and PPi. Shows higher affinity for the full-length tRNA(Thr) lacking only the t(6)A37 modification than for its fully modified counterpart. Could also be required for the maturation of 16S rRNA. Binds to double-stranded RNA but does not interact tightly with either of the ribosomal subunits, or the 70S particles.[HAMAP-Rule:MF_01852]<ref>PMID:15716138</ref> <ref>PMID:19287007</ref> <ref>PMID:21285948</ref> <ref>PMID:22378793</ref> <ref>PMID:23072323</ref>
| + | [https://www.uniprot.org/uniprot/TSAC_ECOLI TSAC_ECOLI] Required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. Catalyzes the conversion of L-threonine, bicarbonate/CO(2) and ATP to give threonylcarbamoyl-AMP (TC-AMP) as the acyladenylate intermediate, with the release of pyrophosphate. Is also able to catalyze the reverse reaction in vitro, i.e. the formation of ATP from TC-AMP and PPi. Shows higher affinity for the full-length tRNA(Thr) lacking only the t(6)A37 modification than for its fully modified counterpart. Could also be required for the maturation of 16S rRNA. Binds to double-stranded RNA but does not interact tightly with either of the ribosomal subunits, or the 70S particles.[HAMAP-Rule:MF_01852]<ref>PMID:15716138</ref> <ref>PMID:19287007</ref> <ref>PMID:21285948</ref> <ref>PMID:22378793</ref> <ref>PMID:23072323</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: L-threonylcarbamoyladenylate synthase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Agris, P F]] | + | [[Category: Agris PF]] |
| - | [[Category: Bilbille, Y]] | + | [[Category: Bilbille Y]] |
| - | [[Category: Bobay, B G]] | + | [[Category: Bobay BG]] |
| - | [[Category: Deutsch, C]] | + | [[Category: Deutsch C]] |
| - | [[Category: Harris, K A]] | + | [[Category: Harris KA]] |
| - | [[Category: Iwata-Reuyl, D]] | + | [[Category: Iwata-Reuyl D]] |
| - | [[Category: Sarachan, K L]] | + | [[Category: Sarachan KL]] |
| - | [[Category: Sims, A F]] | + | [[Category: Sims AF]] |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
TSAC_ECOLI Required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. Catalyzes the conversion of L-threonine, bicarbonate/CO(2) and ATP to give threonylcarbamoyl-AMP (TC-AMP) as the acyladenylate intermediate, with the release of pyrophosphate. Is also able to catalyze the reverse reaction in vitro, i.e. the formation of ATP from TC-AMP and PPi. Shows higher affinity for the full-length tRNA(Thr) lacking only the t(6)A37 modification than for its fully modified counterpart. Could also be required for the maturation of 16S rRNA. Binds to double-stranded RNA but does not interact tightly with either of the ribosomal subunits, or the 70S particles.[HAMAP-Rule:MF_01852][1] [2] [3] [4] [5]
Publication Abstract from PubMed
The hypermodified nucleoside N6-threonylcarbamoyladenosine (t6A37) is present in many distinct tRNA species and has been found in organisms in all domains of life. This post-transcriptional modification enhances translation fidelity by stabilizing the anticodon-codon interaction in the ribosomal decoding site. The biosynthetic pathway of t6A37 is complex and not well understood. In bacteria, four proteins have been discovered to be both required and sufficient for t6A37 modification: TsaC, TsaD, TsaB and TsaE. Of these, TsaC and TsaD are members of universally conserved protein families. Although TsaC has been shown to catalyze the formation of L-threonylcarbamoyl-AMP (TC-AMP), a key intermediate in the biosynthesis of t6A37, the details of the enzymatic mechanism remain unsolved. Therefore, the solution structure of Escherichia coli TsaC was characterized by NMR in order to further study the interactions with ATP and L-threonine, both substrates of TsaC in the biosynthesis of TC-AMP. Several conserved amino acids were identified that create a hydrophobic binding pocket for the adenine of ATP. Additionally, two residues were found to interact with L-threonine. Both binding sites are located in a deep cavity at the center of the protein. Models derived from the NMR data and molecular modeling reveal several sites with considerable conformational flexibility in TsaC that may be important for L-threonine recognition, ATP activation and/or protein-protein interactions. These observations further the understanding of the enzymatic reaction catalyzed by TsaC, a threonylcarbamoyl-AMP synthase, and provide structure-based insight into the mechanism of t6A37 biosynthesis.
NMR-based structural analysis of threonylcarbamoyl-AMP synthase and its substrate interactions.,Harris KA, Bobay BG, Sarachan KL, Sims AF, Bilbille Y, Deutsch C, Iwata-Reuyl D, Agris PF J Biol Chem. 2015 Jun 9. pii: jbc.M114.631242. PMID:26060251[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kaczanowska M, Ryden-Aulin M. The YrdC protein--a putative ribosome maturation factor. Biochim Biophys Acta. 2005 Feb 14;1727(2):87-96. Epub 2004 Dec 31. PMID:15716138 doi:http://dx.doi.org/S0167-4781(04)00263-5
- ↑ El Yacoubi B, Lyons B, Cruz Y, Reddy R, Nordin B, Agnelli F, Williamson JR, Schimmel P, Swairjo MA, de Crecy-Lagard V. The universal YrdC/Sua5 family is required for the formation of threonylcarbamoyladenosine in tRNA. Nucleic Acids Res. 2009 May;37(9):2894-909. doi: 10.1093/nar/gkp152. Epub 2009, Mar 13. PMID:19287007 doi:http://dx.doi.org/10.1093/nar/gkp152
- ↑ El Yacoubi B, Hatin I, Deutsch C, Kahveci T, Rousset JP, Iwata-Reuyl D, Murzin AG, de Crecy-Lagard V. A role for the universal Kae1/Qri7/YgjD (COG0533) family in tRNA modification. EMBO J. 2011 Mar 2;30(5):882-93. doi: 10.1038/emboj.2010.363. Epub 2011 Feb 1. PMID:21285948 doi:10.1038/emboj.2010.363
- ↑ Deutsch C, El Yacoubi B, de Crecy-Lagard V, Iwata-Reuyl D. Biosynthesis of threonylcarbamoyl adenosine (t6A), a universal tRNA nucleoside. J Biol Chem. 2012 Apr 20;287(17):13666-73. doi: 10.1074/jbc.M112.344028. Epub, 2012 Feb 29. PMID:22378793 doi:http://dx.doi.org/10.1074/jbc.M112.344028
- ↑ Lauhon CT. Mechanism of N6-threonylcarbamoyladenonsine (t(6)A) biosynthesis: isolation and characterization of the intermediate threonylcarbamoyl-AMP. Biochemistry. 2012 Nov 6;51(44):8950-63. doi: 10.1021/bi301233d. Epub 2012 Oct, 26. PMID:23072323 doi:http://dx.doi.org/10.1021/bi301233d
- ↑ Harris KA, Bobay BG, Sarachan KL, Sims AF, Bilbille Y, Deutsch C, Iwata-Reuyl D, Agris PF. NMR-based structural analysis of threonylcarbamoyl-AMP synthase and its substrate interactions. J Biol Chem. 2015 Jun 9. pii: jbc.M114.631242. PMID:26060251 doi:http://dx.doi.org/10.1074/jbc.M114.631242
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