FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4245655245> ?p ?o ?g. }

• W4245655245 abstract "Ketoreductase enzymes (KRs) with a high degree of regio- and stereoselectivity are useful biocatalysts for the production of small, specific chiral alcohols from achiral ketones. Actinorhodin KR (<i>act</i>KR), part of a type II polyketide synthase involved in the biosynthesis of the antibiotic actinorhodin, can also turn over small ketones. <i>In vitro</i> studies assessing stereocontrol in <i>act</i>KR have found that, in the “reverse” direction, the wild-type (WT) enzyme’s mild preference for <i>S-α</i>-tetralol is enhanced in certain mutants (<i>e.g.</i> P94L); and entirely reversed in others (<i>e.g.</i> V151L) in favor of <i>R-α</i>-tetralol. Here, we employ efficient atomistic simulations to rationalize these trends in WT, P94L, and V151L <i>act</i>KR, using <i>trans-</i>1-decalone (<b>1</b>) as the model substrate. Three potential factors (<b>FI</b>-<b>FIII</b>) are investigated: frequency of <i>pro-R</i> <i>vs.</i> <i>pro-S</i> reactive poses (<b>FI</b>) is assessed with classical molecular dynamics (MD); binding affinity of <i>pro-R</i> <i>vs.</i> <i>pro-S</i> orientations (<b>FII</b>) is compared using the binding free energy method MM/PBSA; and differences in reaction barriers towards <i>trans-</i>1-decalol (<b>FIII</b>) are assessed by hybrid semiempirical quantum / classical (QM/MM) MD simulations with umbrella sampling, benchmarked with density functional theory. No single factor is found to dominate stereocontrol: <b>FI</b> largely determines the selectivity of V151L <i>act</i>KR, whereas <b>FIII</b> is more dominant in the case of P94L. It is also found that formation of <i>S-trans-</i>1-decalol or <i>R-trans-</i>1-decalol mainly arises from the reduction of the <i>trans</i>-1-decalone enantiomers <i>(4aS,8aR)</i>-<b>1</b> or <i>(4aR,8aS)</i>-<b>1</b>, respectively. Our work highlights the complexity of enzyme stereoselectivity as well as the usefulness of atomistic simulations to aid the design of stereoselective biocatalysts." @default.
• W4245655245 created "2022-05-12" @default.
• W4245655245 creator A5002270644 @default.
• W4245655245 creator A5087676999 @default.
• W4245655245 date "2018-12-04" @default.
• W4245655245 modified "2023-09-25" @default.
• W4245655245 title "Unpicking the Cause of Stereoselectivity in Actinorhodin Ketoreductase Variants with Atomistic Simulations" @default.
• W4245655245 doi "https://doi.org/10.26434/chemrxiv.7358663" @default.
• W4245655245 hasPublicationYear "2018" @default.
• W4245655245 type Work @default.
• W4245655245 citedByCount "0" @default.
• W4245655245 crossrefType "posted-content" @default.
• W4245655245 hasAuthorship W4245655245A5002270644 @default.
• W4245655245 hasAuthorship W4245655245A5087676999 @default.
• W4245655245 hasBestOaLocation W42456552451 @default.
• W4245655245 hasConcept C161790260 @default.
• W4245655245 hasConcept C181199279 @default.
• W4245655245 hasConcept C181647583 @default.
• W4245655245 hasConcept C185592680 @default.
• W4245655245 hasConcept C2776668381 @default.
• W4245655245 hasConcept C2778635478 @default.
• W4245655245 hasConcept C553450214 @default.
• W4245655245 hasConcept C55493867 @default.
• W4245655245 hasConcept C71240020 @default.
• W4245655245 hasConceptScore W4245655245C161790260 @default.
• W4245655245 hasConceptScore W4245655245C181199279 @default.
• W4245655245 hasConceptScore W4245655245C181647583 @default.
• W4245655245 hasConceptScore W4245655245C185592680 @default.
• W4245655245 hasConceptScore W4245655245C2776668381 @default.
• W4245655245 hasConceptScore W4245655245C2778635478 @default.
• W4245655245 hasConceptScore W4245655245C553450214 @default.
• W4245655245 hasConceptScore W4245655245C55493867 @default.
• W4245655245 hasConceptScore W4245655245C71240020 @default.
• W4245655245 hasLocation W42456552451 @default.
• W4245655245 hasLocation W42456552452 @default.
• W4245655245 hasLocation W42456552453 @default.
• W4245655245 hasOpenAccess W4245655245 @default.
• W4245655245 hasPrimaryLocation W42456552451 @default.
• W4245655245 hasRelatedWork W1570438659 @default.
• W4245655245 hasRelatedWork W1968027627 @default.
• W4245655245 hasRelatedWork W2020748792 @default.
• W4245655245 hasRelatedWork W2031765841 @default.
• W4245655245 hasRelatedWork W2041315493 @default.
• W4245655245 hasRelatedWork W2041467484 @default.
• W4245655245 hasRelatedWork W2122051308 @default.
• W4245655245 hasRelatedWork W2953110814 @default.
• W4245655245 hasRelatedWork W2953363697 @default.
• W4245655245 hasRelatedWork W4223473760 @default.
• W4245655245 isParatext "false" @default.
• W4245655245 isRetracted "false" @default.
• W4245655245 workType "article" @default.