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| | <StructureSection load='3kfl' size='340' side='right'caption='[[3kfl]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='3kfl' size='340' side='right'caption='[[3kfl]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3kfl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leima Leima]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KFL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3kfl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_major Leishmania major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KFL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=ME8:[[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHOXY-HYDROXY-PHOSPHORYL]+(2S)-2-AZANYL-4-METHYLSULFANYL-BUTANOATE'>ME8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</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]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LmjF21.0810, MetRS ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5664 LEIMA])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=ME8:[[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHOXY-HYDROXY-PHOSPHORYL]+(2S)-2-AZANYL-4-METHYLSULFANYL-BUTANOATE'>ME8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methionine--tRNA_ligase Methionine--tRNA ligase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.10 6.1.1.10] </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=3kfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kfl OCA], [https://pdbe.org/3kfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kfl RCSB], [https://www.ebi.ac.uk/pdbsum/3kfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kfl ProSAT]</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=3kfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kfl OCA], [https://pdbe.org/3kfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kfl RCSB], [https://www.ebi.ac.uk/pdbsum/3kfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kfl ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q4QCD2_LEIMA Q4QCD2_LEIMA] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Leima]] | + | [[Category: Leishmania major]] |
| - | [[Category: Methionine--tRNA ligase]]
| + | [[Category: Larson ET]] |
| - | [[Category: Larson, E T]] | + | [[Category: Merritt EA]] |
| - | [[Category: Structural genomic]]
| + | |
| - | [[Category: Merritt, E A]] | + | |
| - | [[Category: Aar]]
| + | |
| - | [[Category: Aminoacyl-trna synthetase]]
| + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Leishmania]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Methionine]]
| + | |
| - | [[Category: Metr]]
| + | |
| - | [[Category: Msgpp]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Parasite]]
| + | |
| - | [[Category: Translation]]
| + | |
| - | [[Category: Trna ligase]]
| + | |
| Structural highlights
3kfl is a 1 chain structure with sequence from Leishmania major. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q4QCD2_LEIMA
Publication Abstract from PubMed
Leishmania parasites cause two million new cases of leishmaniasis each year with several hundreds of millions of people at risk. Due to the paucity and shortcomings of available drugs, we have undertaken the crystal structure determination of a key enzyme from Leishmania major in hopes of creating a platform for the rational design of new therapeutics. Crystals of the catalytic core of methionyl-tRNA synthetase from L. major (LmMetRS) were obtained with the substrates MgATP and methionine present in the crystallization medium. These crystals yielded the 2.0 A resolution structure of LmMetRS in complex with two products, methionyladenylate and pyrophosphate, along with a Mg(2+) ion that bridges them. This is the first class I aminoacyl-tRNA synthetase (aaRS) structure with pyrophosphate bound. The residues of the class I aaRS signature sequence motifs, KISKS and HIGH, make numerous contacts with the pyrophosphate. Substantial differences between the LmMetRS structure and previously reported complexes of Escherichia coli MetRS (EcMetRS) with analogs of the methionyladenylate intermediate product are observed, even though one of these analogs only differs by one atom from the intermediate. The source of these structural differences is attributed to the presence of the product pyrophosphate in LmMetRS. Analysis of the LmMetRS structure in light of the Aquifex aeolicus MetRS-tRNA(Met) complex shows that major rearrangements of multiple structural elements of enzyme and/or tRNA are required to allow the CCA acceptor triplet to reach the methionyladenylate intermediate in the active site. Comparison with sequences of human cytosolic and mitochondrial MetRS reveals interesting differences near the ATP- and methionine-binding regions of LmMetRS, suggesting that it should be possible to obtain compounds that selectively inhibit the parasite enzyme.
Structure of Leishmania major methionyl-tRNA synthetase in complex with intermediate products methionyladenylate and pyrophosphate.,Larson ET, Kim JE, Zucker FH, Kelley A, Mueller N, Napuli AJ, Verlinde CL, Fan E, Buckner FS, Van Voorhis WC, Merritt EA, Hol WG Biochimie. 2011 Mar;93(3):570-82. Epub 2010 Dec 7. PMID:21144880[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Larson ET, Kim JE, Zucker FH, Kelley A, Mueller N, Napuli AJ, Verlinde CL, Fan E, Buckner FS, Van Voorhis WC, Merritt EA, Hol WG. Structure of Leishmania major methionyl-tRNA synthetase in complex with intermediate products methionyladenylate and pyrophosphate. Biochimie. 2011 Mar;93(3):570-82. Epub 2010 Dec 7. PMID:21144880 doi:10.1016/j.biochi.2010.11.015
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