|
|
| Line 3: |
Line 3: |
| | <StructureSection load='4k88' size='340' side='right'caption='[[4k88]], [[Resolution|resolution]] 2.62Å' scene=''> | | <StructureSection load='4k88' size='340' side='right'caption='[[4k88]], [[Resolution|resolution]] 2.62Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4k88]] 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=4K88 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K88 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4k88]] 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=4K88 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K88 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HFG:7-BROMO-6-CHLORO-3-{3-[(2R,3S)-3-HYDROXYPIPERIDIN-2-YL]-2-OXOPROPYL}QUINAZOLIN-4(3H)-ONE'>HFG</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=HFG:7-BROMO-6-CHLORO-3-{3-[(2R,3S)-3-HYDROXYPIPERIDIN-2-YL]-2-OXOPROPYL}QUINAZOLIN-4(3H)-ONE'>HFG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k86|4k86]], [[4k87|4k87]]</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=4k88 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k88 OCA], [https://pdbe.org/4k88 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k88 RCSB], [https://www.ebi.ac.uk/pdbsum/4k88 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k88 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EPRS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Proline--tRNA_ligase Proline--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.15 6.1.1.15] </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=4k88 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k88 OCA], [http://pdbe.org/4k88 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k88 RCSB], [http://www.ebi.ac.uk/pdbsum/4k88 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k88 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 28: |
Line 25: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Proline--tRNA ligase]]
| + | [[Category: Hwang KY]] |
| - | [[Category: Hwang, K Y]] | + | [[Category: Lee EH]] |
| - | [[Category: Lee, E H]] | + | [[Category: Son JH]] |
| - | [[Category: Son, J H]] | + | |
| - | [[Category: Class ii trna synthetase]]
| + | |
| - | [[Category: Cytosol]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Ligase-ligase inhibitor complex]]
| + | |
| - | [[Category: Zinc binding]]
| + | |
| 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
Aminoacyl-tRNA synthetases recognize cognate amino acids and tRNAs from their noncognate counterparts and catalyze the formation of aminoacyl-tRNAs. Halofuginone (HF), a coccidiostat used in veterinary medicine, exerts its effects by acting as a high-affinity inhibitor of the enzyme glutamyl-prolyl-tRNA synthetase (EPRS). In order to elucidate the precise molecular basis of this inhibition mechanism of human EPRS, the crystal structures of the prolyl-tRNA synthetase domain of human EPRS (hPRS) at 2.4 A resolution (hPRS-apo), of hPRS complexed with ATP and the substrate proline at 2.3 A resolution (hPRS-sub) and of hPRS complexed with HF at 2.62 A resolution (hPRS-HF) are presented. These structures show plainly that motif 1 functions as a cap in hPRS, which is loosely opened in hPRS-apo, tightly closed in hPRS-sub and incorrectly closed in hPRS-HF. In addition, the structural analyses are consistent with more effective binding of hPRS to HF with ATP. Mutagenesis and biochemical analysis confirmed the key roles of two residues, Phe1097 and Arg1152, in the HF inhibition mechanism. These structures will lead to the development of more potent and selective hPRS inhibitors for promoting inflammatory resolution.
Conformational changes in human prolyl-tRNA synthetase upon binding of the substrates proline and ATP and the inhibitor halofuginone.,Son J, Lee EH, Park M, Kim JH, Kim J, Kim S, Jeon YH, Hwang KY Acta Crystallogr D Biol Crystallogr. 2013 Oct;69(Pt 10):2136-45. doi:, 10.1107/S0907444913020556. Epub 2013 Sep 20. PMID:24100331[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
- ↑ Son J, Lee EH, Park M, Kim JH, Kim J, Kim S, Jeon YH, Hwang KY. Conformational changes in human prolyl-tRNA synthetase upon binding of the substrates proline and ATP and the inhibitor halofuginone. Acta Crystallogr D Biol Crystallogr. 2013 Oct;69(Pt 10):2136-45. doi:, 10.1107/S0907444913020556. Epub 2013 Sep 20. PMID:24100331 doi:http://dx.doi.org/10.1107/S0907444913020556
|
