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| | ==Kinetic and Structural Changes in HsmtPheRS, Induced by Pathogenic Mutations in Human FARS2== | | ==Kinetic and Structural Changes in HsmtPheRS, Induced by Pathogenic Mutations in Human FARS2== |
| - | <StructureSection load='5mgv' size='340' side='right' caption='[[5mgv]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='5mgv' size='340' side='right'caption='[[5mgv]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mgv]] 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=5MGV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MGV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mgv]] 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=5MGV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MGV FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FARS2, FARS1, HSPC320 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.05Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phenylalanine--tRNA_ligase Phenylalanine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.20 6.1.1.20] </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=5mgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgv OCA], [https://pdbe.org/5mgv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mgv RCSB], [https://www.ebi.ac.uk/pdbsum/5mgv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgv 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=5mgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgv OCA], [http://pdbe.org/5mgv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mgv RCSB], [http://www.ebi.ac.uk/pdbsum/5mgv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SYFM_HUMAN SYFM_HUMAN]] Catalyzes direct attachment of p-Tyr (Tyr) to tRNAPhe. Permits also, with a lower efficiency, the attachment of m-Tyr to tRNAPhe, thereby opening the way for delivery of the misacylated tRNA to the ribosome and incorporation of ROS-damaged amino acid into proteins.<ref>PMID:19549855</ref> | + | [https://www.uniprot.org/uniprot/SYFM_HUMAN SYFM_HUMAN] Catalyzes direct attachment of p-Tyr (Tyr) to tRNAPhe. Permits also, with a lower efficiency, the attachment of m-Tyr to tRNAPhe, thereby opening the way for delivery of the misacylated tRNA to the ribosome and incorporation of ROS-damaged amino acid into proteins.<ref>PMID:19549855</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 5mgv" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5mgv" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Phenylalanine--tRNA ligase]] | + | [[Category: Large Structures]] |
| - | [[Category: Chrzanowska-Lightowlers, Z]] | + | [[Category: Chrzanowska-Lightowlers Z]] |
| - | [[Category: Kartvelishvili, E]] | + | [[Category: Kartvelishvili E]] |
| - | [[Category: Moor, N]] | + | [[Category: Moor N]] |
| - | [[Category: Safro, M]] | + | [[Category: Safro M]] |
| - | [[Category: Tworowski, D]] | + | [[Category: Tworowski D]] |
| - | [[Category: Vernon, H]] | + | [[Category: Vernon H]] |
| - | [[Category: Wang, J]] | + | [[Category: Wang J]] |
| - | [[Category: Wong, L J]] | + | [[Category: Wong L-J]] |
| - | [[Category: Aminoacylation]]
| + | |
| - | [[Category: Crystal structure of pathogenic human mitochondrial pher]]
| + | |
| - | [[Category: Kinetik study]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Molecular dynamic]]
| + | |
| Structural highlights
Function
SYFM_HUMAN Catalyzes direct attachment of p-Tyr (Tyr) to tRNAPhe. Permits also, with a lower efficiency, the attachment of m-Tyr to tRNAPhe, thereby opening the way for delivery of the misacylated tRNA to the ribosome and incorporation of ROS-damaged amino acid into proteins.[1]
Publication Abstract from PubMed
Mutations in the mitochondrial aminoacyl-tRNA synthetases (mtaaRSs) can cause profound clinical presentations, and have manifested as diseases with very selective tissue specificity. To date most of the mtaaRS mutations could be phenotypically recognized, such that clinicians could identify the affected mtaaRS from the symptoms alone. Among the recently reported pathogenic variants are point mutations in FARS2 gene, encoding the human mitochondrial PheRS. Patient symptoms range from spastic paraplegia to fatal infantile Alpers encephalopathy. How clinical manifestations of these mutations relate to the changes in three-dimensional structures and kinetic characteristics remains unclear, although impaired aminoacylation has been proposed as possible etiology of diseases. Here, we report four crystal structures of HsmtPheRS mutants, and extensive MD simulations for wild-type and nine mutants to reveal the structural changes on dynamic trajectories of HsmtPheRS. Using steady-state kinetic measurements of phenylalanine activation and tRNAPhe aminoacylation, we gained insight into the structural and kinetic effects of mitochondrial disease-related mutations in FARS2 gene.
Kinetic and structural changes in HsmtPheRS, induced by pathogenic mutations in human FARS2.,Kartvelishvili E, Tworowski D, Vernon H, Moor N, Wang J, Wong LJ, Chrzanowska-Lightowlers Z, Safro M Protein Sci. 2017 Apr 17. doi: 10.1002/pro.3176. PMID:28419689[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Klipcan L, Moor N, Kessler N, Safro MG. Eukaryotic cytosolic and mitochondrial phenylalanyl-tRNA synthetases catalyze the charging of tRNA with the meta-tyrosine. Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11045-8. Epub 2009 Jun 22. PMID:19549855
- ↑ Kartvelishvili E, Tworowski D, Vernon H, Moor N, Wang J, Wong LJ, Chrzanowska-Lightowlers Z, Safro M. Kinetic and structural changes in HsmtPheRS, induced by pathogenic mutations in human FARS2. Protein Sci. 2017 Apr 17. doi: 10.1002/pro.3176. PMID:28419689 doi:http://dx.doi.org/10.1002/pro.3176
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