FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3204158018> ?p ?o ?g. }

• W3204158018 abstract "(KARI) catalyzes the conversion of (S)-2-acetolactate or (S)-2-aceto-2-hydroxybutyrate to 2,3-dihydroxy-3-alkylbutyrate, the second step in the biosynthesis of branched chain amino acids (BCAAs). Because the BCAA biosynthetic pathway is present in bacteria, plants, and fungi, but absent in animals, it is an excellent target for the development of new-generation antibiotics and herbicides. Nevertheless, the mechanism of the KARI-catalyzed reaction has not yet been fully solved. In this study, we used iterative molecular dynamics (MD) flexible fitting-Rosetta techniques to optimize the three-dimensional solution structure of archaea KARI from Sulfolobus solfataricus (Sso-KARI) determined from cryo-electron microscopy. On the basis of the structure of the Sso-KARI/2Mg2+/NADH/(S)-2-acetolactate complex, we deciphered the catalytic mechanism of the KARI-mediated reaction through hybrid quantum mechanics/molecular mechanics MD simulations in conjunction with umbrella sampling. With an activation energy of only 6.06 kcal/mol, a water-mediated, metal-catalyzed, base-induced (WMMCBI) mechanism was preferred for deprotonation of the tertiary OH group of (S)-2-acetolactate in Sso-KARI. The WMMCBI mechanism for double proton transfer occurred within a proton wire route with two steps involving the formation of hydroxide: (i) Glu233 served as a general base to deprotonate the Mg2+-bound water, forming a hydroxide-coordinated Mg2+ ion; (ii) this hydroxide ion acted as a strong base that rapidly deprotonated the ternary OH group of the substrate. In contrast, the direct deprotonation of the substrate by Glu233 was kinetically unfavorable. This mechanism suggests a novel approach for designing catalysts for deprotonation and provides clues for the development of new-generation antibiotics and herbicides." @default.
• W3204158018 created "2021-10-11" @default.
• W3204158018 creator A5040677289 @default.
• W3204158018 creator A5055902301 @default.
• W3204158018 creator A5059704657 @default.
• W3204158018 creator A5076023807 @default.
• W3204158018 date "2021-10-07" @default.
• W3204158018 modified "2023-09-24" @default.
• W3204158018 title "Double Proton Transfer during a Novel Tertiary α-Ketol Rearrangement in Ketol-Acid Reductoisomerase: A Water-Mediated, Metal-Catalyzed, Base-Induced Mechanism" @default.
• W3204158018 cites W1532210859 @default.
• W3204158018 cites W1954932801 @default.
• W3204158018 cites W1963929052 @default.
• W3204158018 cites W1964521061 @default.
• W3204158018 cites W1968213213 @default.
• W3204158018 cites W1978119727 @default.
• W3204158018 cites W1985746019 @default.
• W3204158018 cites W1989753444 @default.
• W3204158018 cites W1993177346 @default.
• W3204158018 cites W1994474796 @default.
• W3204158018 cites W1996956387 @default.
• W3204158018 cites W1997772366 @default.
• W3204158018 cites W2000069011 @default.
• W3204158018 cites W2005723089 @default.
• W3204158018 cites W2009459580 @default.
• W3204158018 cites W2023271753 @default.
• W3204158018 cites W2024872256 @default.
• W3204158018 cites W2025020202 @default.
• W3204158018 cites W2027990790 @default.
• W3204158018 cites W2029194011 @default.
• W3204158018 cites W2038758364 @default.
• W3204158018 cites W2052573265 @default.
• W3204158018 cites W2058807540 @default.
• W3204158018 cites W2059844062 @default.
• W3204158018 cites W2060433756 @default.
• W3204158018 cites W2060872117 @default.
• W3204158018 cites W2061664724 @default.
• W3204158018 cites W2065766058 @default.
• W3204158018 cites W2067718414 @default.
• W3204158018 cites W2074319606 @default.
• W3204158018 cites W2089136101 @default.
• W3204158018 cites W2089638270 @default.
• W3204158018 cites W2101532592 @default.
• W3204158018 cites W2117404759 @default.
• W3204158018 cites W2117458899 @default.
• W3204158018 cites W2141838908 @default.
• W3204158018 cites W2143981217 @default.
• W3204158018 cites W2147775148 @default.
• W3204158018 cites W2150981663 @default.
• W3204158018 cites W2153738830 @default.
• W3204158018 cites W2160294964 @default.
• W3204158018 cites W2280552117 @default.
• W3204158018 cites W2315287708 @default.
• W3204158018 cites W2345658643 @default.
• W3204158018 cites W2581825143 @default.
• W3204158018 cites W2739439285 @default.
• W3204158018 cites W2764128006 @default.
• W3204158018 cites W2791922616 @default.
• W3204158018 cites W2891773955 @default.
• W3204158018 cites W2904460608 @default.
• W3204158018 cites W2913985885 @default.
• W3204158018 cites W2939301327 @default.
• W3204158018 cites W2982193545 @default.
• W3204158018 cites W2998156093 @default.
• W3204158018 cites W3006487582 @default.
• W3204158018 cites W347826878 @default.
• W3204158018 cites W4231183412 @default.
• W3204158018 cites W4245268521 @default.
• W3204158018 doi "https://doi.org/10.1021/acs.jpcb.1c07137" @default.
• W3204158018 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34618450" @default.
• W3204158018 hasPublicationYear "2021" @default.
• W3204158018 type Work @default.
• W3204158018 sameAs 3204158018 @default.
• W3204158018 citedByCount "2" @default.
• W3204158018 countsByYear W32041580182022 @default.
• W3204158018 crossrefType "journal-article" @default.
• W3204158018 hasAuthorship W3204158018A5040677289 @default.
• W3204158018 hasAuthorship W3204158018A5055902301 @default.
• W3204158018 hasAuthorship W3204158018A5059704657 @default.
• W3204158018 hasAuthorship W3204158018A5076023807 @default.
• W3204158018 hasConcept C104317684 @default.
• W3204158018 hasConcept C118629725 @default.
• W3204158018 hasConcept C145148216 @default.
• W3204158018 hasConcept C161790260 @default.
• W3204158018 hasConcept C178790620 @default.
• W3204158018 hasConcept C185592680 @default.
• W3204158018 hasConcept C2775896084 @default.
• W3204158018 hasConcept C2777626080 @default.
• W3204158018 hasConcept C2780631447 @default.
• W3204158018 hasConcept C550995028 @default.
• W3204158018 hasConcept C55493867 @default.
• W3204158018 hasConcept C63338738 @default.
• W3204158018 hasConcept C71240020 @default.
• W3204158018 hasConcept C8010536 @default.
• W3204158018 hasConceptScore W3204158018C104317684 @default.
• W3204158018 hasConceptScore W3204158018C118629725 @default.
• W3204158018 hasConceptScore W3204158018C145148216 @default.
• W3204158018 hasConceptScore W3204158018C161790260 @default.
• W3204158018 hasConceptScore W3204158018C178790620 @default.
• W3204158018 hasConceptScore W3204158018C185592680 @default.
• W3204158018 hasConceptScore W3204158018C2775896084 @default.

• next