7twl: Difference between revisions
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==Structure of a borosin methyltransferase from Mycena rosella with peptide A2 (MroMA2) in complex with SAH== | |||
<StructureSection load='7twl' size='340' side='right'caption='[[7twl]], [[Resolution|resolution]] 1.86Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7twl]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycena_rosella Mycena rosella]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TWL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TWL 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]] 1.86Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=7twl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7twl OCA], [https://pdbe.org/7twl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7twl RCSB], [https://www.ebi.ac.uk/pdbsum/7twl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7twl ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
N-methylation of peptide backbones has often been utilized as a strategy towards the development of peptidic drugs. However, difficulties in the chemical synthesis, high cost of enantiopure N-methyl building blocks, and subsequent coupling inefficiencies have hampered larger-scale medicinal chemical efforts. Here, we present a chemoenzymatic strategy for backbone N-methylation by bioconjugation of peptides of interest to the catalytic scaffold of a borosin-type methyltransferase. Crystal structures of a substrate tolerant enzyme from Mycena rosella guided the design of a decoupled catalytic scaffold that can be linked via a heterobifunctional crosslinker to any peptide substrate of choice. Peptides linked to the scaffold, including those with non-proteinogenic residues, show robust backbone N-methylation. Various crosslinking strategies were tested to facilitate substrate disassembly, which enabled a reversible bioconjugation approach that efficiently released modified peptide. Our results provide general framework for the backbone N-methylation on any peptide of interest and may facilitate the production of large libraries of N-methylated peptides. | |||
Bioconjugate Platform for Iterative Backbone N-Methylation of Peptides.,Zheng Y, Ongpipattanakul C, Nair SK ACS Catal. 2022 Nov 18;12(22):14006-14014. doi: 10.1021/acscatal.2c04681. Epub , 2022 Oct 31. PMID:36793448<ref>PMID:36793448</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7twl" style="background-color:#fffaf0;"></div> | ||
[[Category: Nair | == References == | ||
[[Category: Ongpipattanakul | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycena rosella]] | |||
[[Category: Nair SK]] | |||
[[Category: Ongpipattanakul C]] | |||
[[Category: Zheng Y]] | |||
Latest revision as of 09:37, 9 October 2024
Structure of a borosin methyltransferase from Mycena rosella with peptide A2 (MroMA2) in complex with SAH
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