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==Engineered sperm whale myoglobin-based carbene transferase== | |||
<StructureSection load='6m8f' size='340' side='right'caption='[[6m8f]], [[Resolution|resolution]] 1.10Å' scene=''> | |||
== Structural highlights == | |||
<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='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'>[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> | |||
== 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;"> | |||
== Publication Abstract from PubMed == | |||
Recent 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<ref>PMID:31134138</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6m8f" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
*[[Myoglobin 3D structures|Myoglobin 3D structures]] | |||
*[[Pepsin|Pepsin]] | |||
*[[Proteinase 3D structures|Proteinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Physeter catodon]] | |||
[[Category: Ando N]] | |||
[[Category: Bacik JP]] | |||
[[Category: Fasan R]] | |||