|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5v58' size='340' side='right'caption='[[5v58]], [[Resolution|resolution]] 2.59Å' scene=''> | | <StructureSection load='5v58' size='340' side='right'caption='[[5v58]], [[Resolution|resolution]] 2.59Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5v58]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V58 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V58 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5v58]] is a 1 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=5V58 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V58 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8X1:5-O-{[(2S)-azetidine-2-carbonyl]sulfamoyl}adenosine'>8X1</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.59Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5v59|5v59]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8X1:5-O-{[(2S)-azetidine-2-carbonyl]sulfamoyl}adenosine'>8X1</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EPRS, GLNS, PARS, QARS, QPRS, PIG32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5v58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v58 OCA], [https://pdbe.org/5v58 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v58 RCSB], [https://www.ebi.ac.uk/pdbsum/5v58 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v58 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=5v58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v58 OCA], [http://pdbe.org/5v58 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v58 RCSB], [http://www.ebi.ac.uk/pdbsum/5v58 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v58 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SYEP_HUMAN SYEP_HUMAN]] Catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the multisynthetase complex and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.<ref>PMID:1756734</ref> <ref>PMID:15479637</ref> <ref>PMID:23071094</ref> | + | [https://www.uniprot.org/uniprot/SYEP_HUMAN SYEP_HUMAN] Catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the multisynthetase complex and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.<ref>PMID:1756734</ref> <ref>PMID:15479637</ref> <ref>PMID:23071094</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 27: |
Line 26: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Schimmel, P]] | + | [[Category: Schimmel P]] |
| - | [[Category: Song, Y]] | + | [[Category: Song Y]] |
| - | [[Category: Zhou, H]] | + | [[Category: Zhou H]] |
| - | [[Category: Aminoacyl-trna synthetase]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Non-proteinogenic amino acid]]
| + | |
| Structural highlights
Function
SYEP_HUMAN Catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the multisynthetase complex and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.[1] [2] [3]
Publication Abstract from PubMed
Hundreds of non-proteinogenic (np) amino acids (AA) are found in plants and can in principle enter human protein synthesis through foods. While aminoacyl-tRNA synthetase (AARS) editing potentially provides a mechanism to reject np AAs, some have pathological associations. Co-crystal structures show that vegetable-sourced azetidine-2-carboxylic acid (Aze), a dual mimic of proline and alanine, is activated by both human prolyl- and alanyl-tRNA synthetases. However, it inserts into proteins as proline, with toxic consequences in vivo. Thus, dual mimicry increases odds for mistranslation through evasion of one but not both tRNA synthetase editing systems.
Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid.,Song Y, Zhou H, Vo MN, Shi Y, Nawaz MH, Vargas-Rodriguez O, Diedrich JK, Yates JR, Kishi S, Musier-Forsyth K, Schimmel P Nat Commun. 2017 Dec 22;8(1):2281. doi: 10.1038/s41467-017-02201-z. PMID:29273753[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cerini C, Kerjan P, Astier M, Gratecos D, Mirande M, Semeriva M. A component of the multisynthetase complex is a multifunctional aminoacyl-tRNA synthetase. EMBO J. 1991 Dec;10(13):4267-77. PMID:1756734
- ↑ Sampath P, Mazumder B, Seshadri V, Gerber CA, Chavatte L, Kinter M, Ting SM, Dignam JD, Kim S, Driscoll DM, Fox PL. Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific silencing of translation. Cell. 2004 Oct 15;119(2):195-208. PMID:15479637 doi:http://dx.doi.org/10.1016/j.cell.2004.09.030
- ↑ Arif A, Chatterjee P, Moodt RA, Fox PL. Heterotrimeric GAIT complex drives transcript-selective translation inhibition in murine macrophages. Mol Cell Biol. 2012 Dec;32(24):5046-55. doi: 10.1128/MCB.01168-12. Epub 2012 Oct , 15. PMID:23071094 doi:10.1128/MCB.01168-12
- ↑ Song Y, Zhou H, Vo MN, Shi Y, Nawaz MH, Vargas-Rodriguez O, Diedrich JK, Yates JR, Kishi S, Musier-Forsyth K, Schimmel P. Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid. Nat Commun. 2017 Dec 22;8(1):2281. doi: 10.1038/s41467-017-02201-z. PMID:29273753 doi:http://dx.doi.org/10.1038/s41467-017-02201-z
|
