FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2025254342> ?p ?o ?g. }

• W2025254342 endingPage "7118" @default.
• W2025254342 startingPage "7104" @default.
• W2025254342 abstract "Assignment of particular roles to catalytic residues is an important requirement in clearly understanding enzyme functions. Therefore, predicting the catalytic activities of mutant variants is a fundamental challenge in computational biochemistry. Although site-directed mutagenesis is widely used for studying enzymatic activities and other important classes of protein function, interpreting mutation experiments is usually difficult mainly due to side effects induced by point mutations. Because steric and, in many cases, electrostatic effects may affect the local, fine geometries conserved in wild-type proteins that are usually believed to be thermodynamically stable, simply reducing a loss in catalytic activity into clear elements is difficult. To address these important but difficult issues, we performed a systematic ab initio QM/MM computational analysis combined with MD-FEP simulations and all-electron QM calculations for the entire protein matrix. We selected chorismate mutase, one of the simplest and well-known enzymes, to discuss the details of mutational effects on the enzymatic reaction process. On the basis of the reliable free energy profiles of the wild-type enzyme and several mutant variants, we analyzed the effects of point mutations relative to electronic structure and protein dynamics. In general, changes in geometrical parameters introduced by a mutation were usually limited to the local mutational site. However, this local structural modification could affect the global protein dynamics through correlated motions of particular amino acid residues even far from the mutation site. Even for mutant reactions with low catalytic activity, transition state stabilization was observed as a result of conformational modifications and reorganization around the active site. As for the electrostatic effect created by the polar protein environment, the wild-type enzyme was most effectively designed to stabilize the transition state of the reactive substrate, and the effect of global polarization in the electronic structure was found to be a small catalytic element during the process. As electrostatic media for optimum catalysis, both wild-type and mutant variant proteins were generally robust against external electrostatic perturbations. Protein structures have a certain flexibility, which allows them to slightly modulate their conformations to maximize the transition state stabilization in response to the steric perturbations induced by mutations." @default.
• W2025254342 created "2016-06-24" @default.
• W2025254342 creator A5056330612 @default.
• W2025254342 date "2010-04-28" @default.
• W2025254342 modified "2023-09-26" @default.
• W2025254342 title "Effects of Point Mutation on Enzymatic Activity: Correlation between Protein Electronic Structure and Motion in Chorismate Mutase Reaction" @default.
• W2025254342 cites W1501974651 @default.
• W2025254342 cites W1568288844 @default.
• W2025254342 cites W1970152696 @default.
• W2025254342 cites W1970988731 @default.
• W2025254342 cites W1975236253 @default.
• W2025254342 cites W1976161355 @default.
• W2025254342 cites W1976499671 @default.
• W2025254342 cites W1977482735 @default.
• W2025254342 cites W1977933444 @default.
• W2025254342 cites W1981986489 @default.
• W2025254342 cites W1982550173 @default.
• W2025254342 cites W1982957428 @default.
• W2025254342 cites W1985889708 @default.
• W2025254342 cites W1988460509 @default.
• W2025254342 cites W1990688676 @default.
• W2025254342 cites W1995500136 @default.
• W2025254342 cites W1998870918 @default.
• W2025254342 cites W2001834673 @default.
• W2025254342 cites W2002150668 @default.
• W2025254342 cites W2004926184 @default.
• W2025254342 cites W2008609697 @default.
• W2025254342 cites W2010740289 @default.
• W2025254342 cites W2012055371 @default.
• W2025254342 cites W2013214522 @default.
• W2025254342 cites W2013253424 @default.
• W2025254342 cites W2013574122 @default.
• W2025254342 cites W2015926027 @default.
• W2025254342 cites W2015993457 @default.
• W2025254342 cites W2016380870 @default.
• W2025254342 cites W2017032574 @default.
• W2025254342 cites W2017835622 @default.
• W2025254342 cites W2022189885 @default.
• W2025254342 cites W2022950330 @default.
• W2025254342 cites W2024872256 @default.
• W2025254342 cites W2031109994 @default.
• W2025254342 cites W2036015372 @default.
• W2025254342 cites W2037316156 @default.
• W2025254342 cites W2037684712 @default.
• W2025254342 cites W2039386462 @default.
• W2025254342 cites W2041467079 @default.
• W2025254342 cites W2043429268 @default.
• W2025254342 cites W2043760657 @default.
• W2025254342 cites W2044947801 @default.
• W2025254342 cites W2046440403 @default.
• W2025254342 cites W2046853598 @default.
• W2025254342 cites W2051315164 @default.
• W2025254342 cites W2051423896 @default.
• W2025254342 cites W2051458308 @default.
• W2025254342 cites W2051758787 @default.
• W2025254342 cites W2055212608 @default.
• W2025254342 cites W2056037482 @default.
• W2025254342 cites W2065492796 @default.
• W2025254342 cites W2065920712 @default.
• W2025254342 cites W2068956506 @default.
• W2025254342 cites W2070074810 @default.
• W2025254342 cites W2077227036 @default.
• W2025254342 cites W2077390552 @default.
• W2025254342 cites W2081077157 @default.
• W2025254342 cites W2083861697 @default.
• W2025254342 cites W2085695161 @default.
• W2025254342 cites W2086634221 @default.
• W2025254342 cites W2088713131 @default.
• W2025254342 cites W2090380768 @default.
• W2025254342 cites W2092956715 @default.
• W2025254342 cites W2095148640 @default.
• W2025254342 cites W2101217381 @default.
• W2025254342 cites W2106140689 @default.
• W2025254342 cites W2108116455 @default.
• W2025254342 cites W2110872379 @default.
• W2025254342 cites W2114941556 @default.
• W2025254342 cites W2115949736 @default.
• W2025254342 cites W2116732424 @default.
• W2025254342 cites W2122199548 @default.
• W2025254342 cites W2134513074 @default.
• W2025254342 cites W2134759124 @default.
• W2025254342 cites W2136913776 @default.
• W2025254342 cites W2138305674 @default.
• W2025254342 cites W2138487150 @default.
• W2025254342 cites W2141838908 @default.
• W2025254342 cites W2149263899 @default.
• W2025254342 cites W2151334055 @default.
• W2025254342 cites W2152220941 @default.
• W2025254342 cites W2152812953 @default.
• W2025254342 cites W2169981389 @default.
• W2025254342 cites W2171596444 @default.
• W2025254342 cites W2171893485 @default.
• W2025254342 cites W2334047574 @default.
• W2025254342 cites W4245335048 @default.
• W2025254342 cites W630005112 @default.
• W2025254342 doi "https://doi.org/10.1021/ja100744h" @default.
• W2025254342 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20426479" @default.
• W2025254342 hasPublicationYear "2010" @default.

• next