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| | ==Crystal Structure of catalytic fragment of E. coli AlaRS G237A in complex with GlySA== | | ==Crystal Structure of catalytic fragment of E. coli AlaRS G237A in complex with GlySA== |
| - | <StructureSection load='3hy0' size='340' side='right' caption='[[3hy0]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='3hy0' size='340' side='right'caption='[[3hy0]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3hy0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HY0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HY0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3hy0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HY0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HY0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=G5A:5-O-(GLYCYLSULFAMOYL)ADENOSINE'>G5A</scene>, <scene name='pdbligand=HED:2-HYDROXYETHYL+DISULFIDE'>HED</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=G5A:5-O-(GLYCYLSULFAMOYL)ADENOSINE'>G5A</scene>, <scene name='pdbligand=HED:2-HYDROXYETHYL+DISULFIDE'>HED</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hxu|3hxu]], [[3hxv|3hxv]], [[3hxw|3hxw]], [[3hxx|3hxx]], [[3hxy|3hxy]], [[3hxz|3hxz]], [[3hy1|3hy1]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3hxu|3hxu]], [[3hxv|3hxv]], [[3hxw|3hxw]], [[3hxx|3hxx]], [[3hxy|3hxy]], [[3hxz|3hxz]], [[3hy1|3hy1]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alaS, lovB, b2697, JW2667 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alaS, lovB, b2697, JW2667 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Alanine--tRNA_ligase Alanine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.7 6.1.1.7] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Alanine--tRNA_ligase Alanine--tRNA ligase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.7 6.1.1.7] </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=3hy0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hy0 OCA], [http://pdbe.org/3hy0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hy0 RCSB], [http://www.ebi.ac.uk/pdbsum/3hy0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hy0 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=3hy0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hy0 OCA], [https://pdbe.org/3hy0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hy0 RCSB], [https://www.ebi.ac.uk/pdbsum/3hy0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hy0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SYA_ECOLI SYA_ECOLI]] Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). AlaRS also incorrectly activates the sterically smaller than alanine amino acid glycine as well as the sterically larger amino acid serine. These incorrectly charged amino acids occur because the of inherent physicochemical limitations on discrimination between closely related amino acids (glycine and serine) in the charging step.<ref>PMID:12554667</ref> <ref>PMID:18723508</ref> <ref>PMID:19661429</ref> Edits incorrectly charged Ser-tRNA(Ala) and Gly-tRNA(Ala) but not incorrectly charged Ser-tRNA(Thr).<ref>PMID:12554667</ref> <ref>PMID:18723508</ref> <ref>PMID:19661429</ref> | + | [[https://www.uniprot.org/uniprot/SYA_ECOLI SYA_ECOLI]] Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). AlaRS also incorrectly activates the sterically smaller than alanine amino acid glycine as well as the sterically larger amino acid serine. These incorrectly charged amino acids occur because the of inherent physicochemical limitations on discrimination between closely related amino acids (glycine and serine) in the charging step.<ref>PMID:12554667</ref> <ref>PMID:18723508</ref> <ref>PMID:19661429</ref> Edits incorrectly charged Ser-tRNA(Ala) and Gly-tRNA(Ala) but not incorrectly charged Ser-tRNA(Thr).<ref>PMID:12554667</ref> <ref>PMID:18723508</ref> <ref>PMID:19661429</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hy/3hy0_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hy/3hy0_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3hy0" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3hy0" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Alanine--tRNA ligase]] | | [[Category: Alanine--tRNA ligase]] |
| | [[Category: Ecoli]] | | [[Category: Ecoli]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Guo, M]] | | [[Category: Guo, M]] |
| | [[Category: Schimmel, P]] | | [[Category: Schimmel, P]] |
| Structural highlights
3hy0 is a 2 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Related: | |
| Gene: | alaS, lovB, b2697, JW2667 (ECOLI) |
| Activity: | Alanine--tRNA ligase, with EC number 6.1.1.7 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[SYA_ECOLI] Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). AlaRS also incorrectly activates the sterically smaller than alanine amino acid glycine as well as the sterically larger amino acid serine. These incorrectly charged amino acids occur because the of inherent physicochemical limitations on discrimination between closely related amino acids (glycine and serine) in the charging step.[1] [2] [3] Edits incorrectly charged Ser-tRNA(Ala) and Gly-tRNA(Ala) but not incorrectly charged Ser-tRNA(Thr).[4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Mistranslation arising from confusion of serine for alanine by alanyl-tRNA synthetases (AlaRSs) has profound functional consequences. Throughout evolution, two editing checkpoints prevent disease-causing mistranslation from confusing glycine or serine for alanine at the active site of AlaRS. In both bacteria and mice, Ser poses a bigger challenge than Gly. One checkpoint is the AlaRS editing centre, and the other is from widely distributed AlaXps-free-standing, genome-encoded editing proteins that clear Ser-tRNA(Ala). The paradox of misincorporating both a smaller (glycine) and a larger (serine) amino acid suggests a deep conflict for nature-designed AlaRS. Here we show the chemical basis for this conflict. Nine crystal structures, together with kinetic and mutational analysis, provided snapshots of adenylate formation for each amino acid. An inherent dilemma is posed by constraints of a structural design that pins down the alpha-amino group of the bound amino acid by using an acidic residue. This design, dating back more than 3 billion years, creates a serendipitous interaction with the serine OH that is difficult to avoid. Apparently because no better architecture for the recognition of alanine could be found, the serine misactivation problem was solved through free-standing AlaXps, which appeared contemporaneously with early AlaRSs. The results reveal unconventional problems and solutions arising from the historical design of the protein synthesis machinery.
Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma.,Guo M, Chong YE, Shapiro R, Beebe K, Yang XL, Schimmel P Nature. 2009 Dec 10;462(7274):808-12. PMID:20010690[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Beebe K, Ribas De Pouplana L, Schimmel P. Elucidation of tRNA-dependent editing by a class II tRNA synthetase and significance for cell viability. EMBO J. 2003 Feb 3;22(3):668-75. PMID:12554667 doi:10.1093/emboj/cdg065
- ↑ Chong YE, Yang XL, Schimmel P. Natural homolog of tRNA synthetase editing domain rescues conditional lethality caused by mistranslation. J Biol Chem. 2008 Oct 31;283(44):30073-8. doi: 10.1074/jbc.M805943200. Epub 2008 , Aug 22. PMID:18723508 doi:10.1074/jbc.M805943200
- ↑ Guo M, Chong YE, Beebe K, Shapiro R, Yang XL, Schimmel P. The C-Ala domain brings together editing and aminoacylation functions on one tRNA. Science. 2009 Aug 7;325(5941):744-7. PMID:19661429 doi:325/5941/744
- ↑ Beebe K, Ribas De Pouplana L, Schimmel P. Elucidation of tRNA-dependent editing by a class II tRNA synthetase and significance for cell viability. EMBO J. 2003 Feb 3;22(3):668-75. PMID:12554667 doi:10.1093/emboj/cdg065
- ↑ Chong YE, Yang XL, Schimmel P. Natural homolog of tRNA synthetase editing domain rescues conditional lethality caused by mistranslation. J Biol Chem. 2008 Oct 31;283(44):30073-8. doi: 10.1074/jbc.M805943200. Epub 2008 , Aug 22. PMID:18723508 doi:10.1074/jbc.M805943200
- ↑ Guo M, Chong YE, Beebe K, Shapiro R, Yang XL, Schimmel P. The C-Ala domain brings together editing and aminoacylation functions on one tRNA. Science. 2009 Aug 7;325(5941):744-7. PMID:19661429 doi:325/5941/744
- ↑ Guo M, Chong YE, Shapiro R, Beebe K, Yang XL, Schimmel P. Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma. Nature. 2009 Dec 10;462(7274):808-12. PMID:20010690 doi:10.1038/nature08612
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