6m8f: Difference between revisions
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<StructureSection load='6m8f' size='340' side='right'caption='[[6m8f]], [[Resolution|resolution]] 1.10Å' scene=''> | <StructureSection load='6m8f' size='340' side='right'caption='[[6m8f]], [[Resolution|resolution]] 1.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6m8f]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6m8f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Physeter_catodon Physeter catodon]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M8F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M8F FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand= | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.1Å</td></tr> | ||
< | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6m8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m8f OCA], [https://pdbe.org/6m8f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m8f RCSB], [https://www.ebi.ac.uk/pdbsum/6m8f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m8f ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/MYG_PHYMC MYG_PHYMC] Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Myoglobin 3D structures|Myoglobin 3D structures]] | |||
*[[Pepsin|Pepsin]] | *[[Pepsin|Pepsin]] | ||
*[[Proteinase|Proteinase]] | *[[Proteinase 3D structures|Proteinase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Physeter catodon]] | ||
[[Category: Ando | [[Category: Ando N]] | ||
[[Category: Bacik | [[Category: Bacik JP]] | ||
[[Category: Fasan | [[Category: Fasan R]] | ||
Latest revision as of 09:26, 11 October 2023
Engineered sperm whale myoglobin-based carbene transferaseEngineered sperm whale myoglobin-based carbene transferase
Structural highlights
FunctionMYG_PHYMC Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles. Publication Abstract from PubMedRecent advances in metalloprotein engineering have led to the development of a myoglobin-based catalyst, Mb(H64V,V68A), capable of promoting the cyclopropanation of vinylarenes with high efficiency and high diastereo- and enantioselectivity. Whereas many enzymes evolved in nature often exhibit catalytic proficiency and exquisite stereoselectivity, how these features are achieved for a non-natural reaction has remained unclear. In this work, the structural determinants responsible for chiral induction and high stereocontrol in Mb(H64V,V68A)-catalyzed cyclopropanation were investigated via a combination of crystallographic, computational (DFT), and structure-activity analyses. Our results show the importance of steric complementarity and non-covalent interactions involving first-sphere active site residues, heme-carbene, and the olefin substrate, in dictating the stereochemical outcome of the cyclopropanation reaction. High stereocontrol is achieved through two major mechanisms. First, by enforcing a specific conformation of the heme-bound carbene within the active site. Second, by controlling the geometry of attack of the olefin on the carbene via steric occlusion, attractive van der Waals forces and protein-mediated pi-pi interactions with the olefin substrate. These insights could be leveraged to expand the substrate scope of the myoglobin-based cyclopropanation catalyst toward non-activated olefins and to increase its cyclopropanation activity in the presence of a bulky alpha-diazo-ester. This work sheds first light into the origin of enzyme-catalyzed enantioselective cyclopropanation, furnishing a mechanistic framework for both understanding the reactivity of current systems and guiding the future development of biological catalysts for this class of synthetically important, abiotic transformations. Origin of high stereocontrol in olefin cyclopropanation catalyzed by an engineered carbene transferase.,Tinoco A, Wei Y, Bacik JP, Carminati DM, Moore EJ, Ando N, Zhang Y, Fasan R ACS Catal. 2019 Feb 1;9(2):1514-1524. doi: 10.1021/acscatal.8b04073. Epub 2018, Dec 28. PMID:31134138[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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