8c49
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of pyrrolysyl-tRNA synthetase from Methanomethylophilus alvus engineered for 3-Methyl-L-histidine, bound to AMPPNP== | |
| + | <StructureSection load='8c49' size='340' side='right'caption='[[8c49]], [[Resolution|resolution]] 1.82Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8c49]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Candidatus_Methanomethylophilus_alvus Candidatus Methanomethylophilus alvus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8C49 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C49 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.82Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></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=8c49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c49 OCA], [https://pdbe.org/8c49 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c49 RCSB], [https://www.ebi.ac.uk/pdbsum/8c49 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c49 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/M9SC49_METAX M9SC49_METAX] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The availability of an expanded genetic code opens exciting new opportunities in enzyme design and engineering. In this regard histidine analogues have proven particularly versatile, serving as ligands to augment metalloenzyme function and as catalytic nucleophiles in designed enzymes. The ability to genetically encode multiple functional residues could greatly expand the range of chemistry accessible within enzyme active sites. Here, we develop mutually orthogonal translation components to selectively encode two structurally similar histidine analogues. Transplanting known mutations from a promiscuous Methanosarcina mazei pyrrolysyl-tRNA synthetase (MmPylRS(IFGFF) ) into a single domain PylRS from Methanomethylophilus alvus (MaPylRS(IFGFF) ) provided a variant with improved efficiency and specificity for 3-methyl-L-histidine (MeHis) incorporation. The MaPylRS(IFGFF) clone was further characterized using in vitro biochemical assays and x-ray crystallography. We subsequently engineered the orthogonal MmPylRS for activity and selectivity for 3-(3-pyridyl)-L-alanine (3-Pyr), which was used in combination with MaPylRS(IFGFF) to produce proteins containing both 3-Pyr and MeHis. Given the versatile roles played by histidine in enzyme mechanisms, we anticipate that the tools developed within this study will underpin the development of enzymes with new and enhanced functions. | ||
| - | + | Engineering mutually orthogonal PylRS/tRNA pairs for dual encoding of functional histidine analogues.,Taylor CJ, Hardy FJ, Burke AJ, Bednar RM, Mehl RA, Green AP, Lovelock SL Protein Sci. 2023 May;32(5):e4640. doi: 10.1002/pro.4640. PMID:37051694<ref>PMID:37051694</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8c49" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Candidatus Methanomethylophilus alvus]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Hardy FJ]] | ||
| + | [[Category: Levy CW]] | ||
Revision as of 06:11, 19 July 2023
Crystal structure of pyrrolysyl-tRNA synthetase from Methanomethylophilus alvus engineered for 3-Methyl-L-histidine, bound to AMPPNP
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