Covalent Anchor Positions Play an Important Role in Tuning Catalytic Properties of a Rationally Designed MnSalen-containing Metalloenzyme
Two questions important to the success in metalloenzyme design are how to attach or anchor metal cofactors inside protein scaffolds, and in what way such positioning affects enzymatic properties. We have previously reported a dual anchoring method to position a nonnative cofactor, MnSalen (1), insid...
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ftpubmed:oai:pubmedcentral.nih.gov:3194002 2023-05-15T18:26:52+02:00 Covalent Anchor Positions Play an Important Role in Tuning Catalytic Properties of a Rationally Designed MnSalen-containing Metalloenzyme Garner, Dewain K. Liang, Lei Barrios, David A. Zhang, Jun-Long Lu, Yi 2011-09-02 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194002 http://www.ncbi.nlm.nih.gov/pubmed/22013554 https://doi.org/10.1021/cs200258e en eng http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194002 http://www.ncbi.nlm.nih.gov/pubmed/22013554 http://dx.doi.org/10.1021/cs200258e Article Text 2011 ftpubmed https://doi.org/10.1021/cs200258e 2013-09-03T21:09:46Z Two questions important to the success in metalloenzyme design are how to attach or anchor metal cofactors inside protein scaffolds, and in what way such positioning affects enzymatic properties. We have previously reported a dual anchoring method to position a nonnative cofactor, MnSalen (1), inside the heme cavity of apo sperm whale myoglobin (Mb) and showed that the dual anchoring can increase both the activity and enantioselectivity over the single anchoring methods, making this artificial enzyme an ideal system to address the above questions. Here we report systematic investigations of the effect of different covalent attachment or anchoring positions on reactivity and selectivity of sulfoxidation by the MnSalen-containing Mb enzymes. We have found that changing the left anchor from Y103C to T39C has an almost identical effect of increasing rate by 1.8-fold and increasing selectivity by +14% for S, whether the right anchor is L72C or S108C. At the same time, regardless of the identity of the left anchor, changing the right anchor from S108C to L72C increases rate by 4-fold and selectivity by +66%. The right anchor site was observed to have a greater influence than the left anchor site on the reactivity and selectivity in sulfoxidation of a wide scope of other ortho-, meta- and para- substituted substrates. The 1•Mb(T39C/L72C) showed the highest reactivity (TON up to 2.31 min-1) and selectivity (ee% up to 83%) among the different anchoring positions examined. Molecular dynamic simulations indicate that these changes in reactivity and selectivity may be due to the steric effects of the linker arms inside the protein cavity. These results indicate that small differences in the anchor positions can result in significant changes in reactivity and enantioselectivity, probably through steric interactions with substrates when they enter the substrate-binding pocket, and that the effects of right and left anchor positions are independent and additive in nature. The finding that the anchoring arms can influence both ... Text Sperm whale PubMed Central (PMC) ACS Catalysis 1 9 1083 1089 |
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Article Garner, Dewain K. Liang, Lei Barrios, David A. Zhang, Jun-Long Lu, Yi Covalent Anchor Positions Play an Important Role in Tuning Catalytic Properties of a Rationally Designed MnSalen-containing Metalloenzyme |
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Article |
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Two questions important to the success in metalloenzyme design are how to attach or anchor metal cofactors inside protein scaffolds, and in what way such positioning affects enzymatic properties. We have previously reported a dual anchoring method to position a nonnative cofactor, MnSalen (1), inside the heme cavity of apo sperm whale myoglobin (Mb) and showed that the dual anchoring can increase both the activity and enantioselectivity over the single anchoring methods, making this artificial enzyme an ideal system to address the above questions. Here we report systematic investigations of the effect of different covalent attachment or anchoring positions on reactivity and selectivity of sulfoxidation by the MnSalen-containing Mb enzymes. We have found that changing the left anchor from Y103C to T39C has an almost identical effect of increasing rate by 1.8-fold and increasing selectivity by +14% for S, whether the right anchor is L72C or S108C. At the same time, regardless of the identity of the left anchor, changing the right anchor from S108C to L72C increases rate by 4-fold and selectivity by +66%. The right anchor site was observed to have a greater influence than the left anchor site on the reactivity and selectivity in sulfoxidation of a wide scope of other ortho-, meta- and para- substituted substrates. The 1•Mb(T39C/L72C) showed the highest reactivity (TON up to 2.31 min-1) and selectivity (ee% up to 83%) among the different anchoring positions examined. Molecular dynamic simulations indicate that these changes in reactivity and selectivity may be due to the steric effects of the linker arms inside the protein cavity. These results indicate that small differences in the anchor positions can result in significant changes in reactivity and enantioselectivity, probably through steric interactions with substrates when they enter the substrate-binding pocket, and that the effects of right and left anchor positions are independent and additive in nature. The finding that the anchoring arms can influence both ... |
format |
Text |
author |
Garner, Dewain K. Liang, Lei Barrios, David A. Zhang, Jun-Long Lu, Yi |
author_facet |
Garner, Dewain K. Liang, Lei Barrios, David A. Zhang, Jun-Long Lu, Yi |
author_sort |
Garner, Dewain K. |
title |
Covalent Anchor Positions Play an Important Role in Tuning Catalytic Properties of a Rationally Designed MnSalen-containing Metalloenzyme |
title_short |
Covalent Anchor Positions Play an Important Role in Tuning Catalytic Properties of a Rationally Designed MnSalen-containing Metalloenzyme |
title_full |
Covalent Anchor Positions Play an Important Role in Tuning Catalytic Properties of a Rationally Designed MnSalen-containing Metalloenzyme |
title_fullStr |
Covalent Anchor Positions Play an Important Role in Tuning Catalytic Properties of a Rationally Designed MnSalen-containing Metalloenzyme |
title_full_unstemmed |
Covalent Anchor Positions Play an Important Role in Tuning Catalytic Properties of a Rationally Designed MnSalen-containing Metalloenzyme |
title_sort |
covalent anchor positions play an important role in tuning catalytic properties of a rationally designed mnsalen-containing metalloenzyme |
publishDate |
2011 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194002 http://www.ncbi.nlm.nih.gov/pubmed/22013554 https://doi.org/10.1021/cs200258e |
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Sperm whale |
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Sperm whale |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194002 http://www.ncbi.nlm.nih.gov/pubmed/22013554 http://dx.doi.org/10.1021/cs200258e |
op_doi |
https://doi.org/10.1021/cs200258e |
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ACS Catalysis |
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