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| | ==crystal structure of the human TGT catalytic subunit QTRT1 in complex with queuine== | | ==crystal structure of the human TGT catalytic subunit QTRT1 in complex with queuine== |
| - | <StructureSection load='6h45' size='340' side='right' caption='[[6h45]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='6h45' size='340' side='right'caption='[[6h45]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6h45]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H45 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H45 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6h45]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H45 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6H45 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GGL:GAMMA-L-GLUTAMIC+ACID'>GGL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=QEI:2-AMINO-5-({[(1S,4S,5R)-4,5-DIHYDROXYCYCLOPENT-2-EN-1-YL]AMINO}METHYL)-3,7-DIHYDRO-4H-PYRROLO[2,3-D]PYRIMIDIN-4-ONE'>QEI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene>, <scene name='pdbligand=QEI:2-AMINO-5-({[(1S,4S,5R)-4,5-DIHYDROXYCYCLOPENT-2-EN-1-YL]AMINO}METHYL)-3,7-DIHYDRO-4H-PYRROLO[2,3-D]PYRIMIDIN-4-ONE'>QEI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></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=6h45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h45 OCA], [https://pdbe.org/6h45 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6h45 RCSB], [https://www.ebi.ac.uk/pdbsum/6h45 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6h45 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/tRNA-guanine(34)_transglycosylase tRNA-guanine(34) transglycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.29 2.4.2.29] </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=6h45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h45 OCA], [http://pdbe.org/6h45 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h45 RCSB], [http://www.ebi.ac.uk/pdbsum/6h45 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h45 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TGT_HUMAN TGT_HUMAN]] Catalytic subunit of the queuine tRNA-ribosyltransferase (TGT) that catalyzes the base-exchange of a guanine (G) residue with queuine (Q) at position 34 (anticodon wobble position) in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr), resulting in the hypermodified nucleoside queuosine (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine) (PubMed:11255023, PubMed:20354154). Catalysis occurs through a double-displacement mechanism. The nucleophile active site attacks the C1' of nucleotide 34 to detach the guanine base from the RNA, forming a covalent enzyme-RNA intermediate. The proton acceptor active site deprotonates the incoming queuine, allowing a nucleophilic attack on the C1' of the ribose to form the product (By similarity).[UniProtKB:P28720][HAMAP-Rule:MF_03218]<ref>PMID:11255023</ref> <ref>PMID:20354154</ref> | + | [https://www.uniprot.org/uniprot/TGT_HUMAN TGT_HUMAN] Catalytic subunit of the queuine tRNA-ribosyltransferase (TGT) that catalyzes the base-exchange of a guanine (G) residue with queuine (Q) at position 34 (anticodon wobble position) in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr), resulting in the hypermodified nucleoside queuosine (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine) (PubMed:11255023, PubMed:20354154). Catalysis occurs through a double-displacement mechanism. The nucleophile active site attacks the C1' of nucleotide 34 to detach the guanine base from the RNA, forming a covalent enzyme-RNA intermediate. The proton acceptor active site deprotonates the incoming queuine, allowing a nucleophilic attack on the C1' of the ribose to form the product (By similarity).[UniProtKB:P28720][HAMAP-Rule:MF_03218]<ref>PMID:11255023</ref> <ref>PMID:20354154</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6h45" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6h45" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[TRNA-guanine transglycosylase 3D structures|TRNA-guanine transglycosylase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ficner, R]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Johannsson, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Neumann, P]] | + | [[Category: Ficner R]] |
| - | [[Category: Queuine]] | + | [[Category: Johannsson S]] |
| - | [[Category: Rna]] | + | [[Category: Neumann P]] |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transglycosylase]]
| + | |
| - | [[Category: Trna]]
| + | |
| Structural highlights
6h45 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
TGT_HUMAN Catalytic subunit of the queuine tRNA-ribosyltransferase (TGT) that catalyzes the base-exchange of a guanine (G) residue with queuine (Q) at position 34 (anticodon wobble position) in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr), resulting in the hypermodified nucleoside queuosine (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine) (PubMed:11255023, PubMed:20354154). Catalysis occurs through a double-displacement mechanism. The nucleophile active site attacks the C1' of nucleotide 34 to detach the guanine base from the RNA, forming a covalent enzyme-RNA intermediate. The proton acceptor active site deprotonates the incoming queuine, allowing a nucleophilic attack on the C1' of the ribose to form the product (By similarity).[UniProtKB:P28720][HAMAP-Rule:MF_03218][1] [2]
Publication Abstract from PubMed
RNA modifications have been implicated in diverse and important roles in all kingdoms of life with over 100 of them present on tRNAs. A prominent modification at the wobble base of four tRNAs is the 7-deaza-guanine derivative queuine which substitutes the guanine at position 34. This exchange is catalyzed by members of the enzyme class of tRNA guanine transglycosylases (TGTs). These enzymes incorporate guanine substituents into tRNA(Asp), tRNA(Asn) tRNA(His), and tRNA(Tyr) in all kingdoms of life. In contrast to the homodimeric bacterial TGT, the active eukaryotic TGT is a heterodimer in solution, comprised of a catalytic QTRT1 subunit and a noncatalytic QTRT2 subunit. Bacterial TGT enzymes, that incorporate a queuine precursor, have been identified or proposed as virulence factors for infections by pathogens in humans and therefore are valuable targets for drug design. To date no structure of a eukaryotic catalytic subunit is reported, and differences to its bacterial counterpart have to be deducted from sequence analysis and models. Here we report the first crystal structure of a eukaryotic QTRT1 subunit and compare it to known structures of the bacterial TGT and murine QTRT2. Furthermore, we were able to determine the crystal structure of QTRT1 in complex with the queuine substrate.
Crystal Structure of the Human tRNA Guanine Transglycosylase Catalytic Subunit QTRT1.,Johannsson S, Neumann P, Ficner R Biomolecules. 2018 Aug 24;8(3). pii: biom8030081. doi: 10.3390/biom8030081. PMID:30149595[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Deshpande KL, Katze JR. Characterization of cDNA encoding the human tRNA-guanine transglycosylase (TGT) catalytic subunit. Gene. 2001 Mar 7;265(1-2):205-12. PMID:11255023
- ↑ Chen YC, Kelly VP, Stachura SV, Garcia GA. Characterization of the human tRNA-guanine transglycosylase: confirmation of the heterodimeric subunit structure. RNA. 2010 May;16(5):958-68. doi: 10.1261/rna.1997610. Epub 2010 Mar 30. PMID:20354154 doi:http://dx.doi.org/10.1261/rna.1997610
- ↑ Johannsson S, Neumann P, Ficner R. Crystal Structure of the Human tRNA Guanine Transglycosylase Catalytic Subunit QTRT1. Biomolecules. 2018 Aug 24;8(3). pii: biom8030081. doi: 10.3390/biom8030081. PMID:30149595 doi:http://dx.doi.org/10.3390/biom8030081
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