FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2051506593> ?p ?o ?g. }

• W2051506593 endingPage "246" @default.
• W2051506593 startingPage "229" @default.
• W2051506593 abstract "Several members of the Alkaline Phosphatase (AP) superfamily exhibit a high level of catalytic proffciency and promiscuity in structurally similar active sites. A thorough characterization of the nature of transition state for different substrates in these enzymes is crucial for understanding the molecular mechanisms that govern those remarkable catalytic properties. In this work, we study the hydrolysis of a phosphate diester, MpNPP(-), in solution, two experimentally well-characterized variants of AP (R166S AP, R166S/E322Y AP) and wild type Nucleotide pyrophosphatase/phosphodiesterase (NPP) by QM/MM calculations in which the QM method is an approximate density functional theory previously parametrized for phosphate hydrolysis (SCC-DFTBPR). The general agreements found between these calculations and available experimental data for both solution and enzymes support the use of SCC-DFTBPR/MM for a semiquantitative analysis of the catalytic mechanism and nature of transition state in AP and NPP. Although phosphate diesters are cognate substrates for NPP but promiscuous substrates for AP, the calculations suggest that their hydrolysis reactions catalyzed by AP and NPP feature similar synchronous transition states that are slightly tighter in nature compared to that in solution, due in part to the geometry of the bimetallic zinc motif. Therefore, this study provides the first direct computational support to the hypothesis that enzymes in the AP superfamily catalyze cognate and promiscuous substrates via similar transition states to those in solution. Our calculations do not support the finding of recent QM/MM studies by López-Canut and co-workers, who suggested that the same diester substrate goes through a much looser transition state in NPP/AP than in solution, a result likely biased by the large structural distortion of the bimetallic zinc site in their simulations. Finally, our calculations for different phosphate diester orientations and phosphorothioate diesters highlight that the interpretation of thio-substitution experiments is not always straightforward." @default.
• W2051506593 created "2016-06-24" @default.
• W2051506593 creator A5027059473 @default.
• W2051506593 creator A5036789652 @default.
• W2051506593 date "2011-12-08" @default.
• W2051506593 modified "2023-09-27" @default.
• W2051506593 title "QM/MM Analysis Suggests That Alkaline Phosphatase (AP) and Nucleotide Pyrophosphatase/Phosphodiesterase Slightly Tighten the Transition State for Phosphate Diester Hydrolysis Relative to Solution: Implication for Catalytic Promiscuity in the AP Superfamily" @default.
• W2051506593 cites W133369315 @default.
• W2051506593 cites W1545545655 @default.
• W2051506593 cites W1954690293 @default.
• W2051506593 cites W1968166922 @default.
• W2051506593 cites W1970790514 @default.
• W2051506593 cites W1972603688 @default.
• W2051506593 cites W1974905452 @default.
• W2051506593 cites W1975945758 @default.
• W2051506593 cites W1976454923 @default.
• W2051506593 cites W1976499671 @default.
• W2051506593 cites W1976883608 @default.
• W2051506593 cites W1977456707 @default.
• W2051506593 cites W1979285357 @default.
• W2051506593 cites W1980363424 @default.
• W2051506593 cites W1981745234 @default.
• W2051506593 cites W1989773022 @default.
• W2051506593 cites W1992625839 @default.
• W2051506593 cites W1993177346 @default.
• W2051506593 cites W1993195149 @default.
• W2051506593 cites W1994103683 @default.
• W2051506593 cites W1995425581 @default.
• W2051506593 cites W1998238795 @default.
• W2051506593 cites W1999938940 @default.
• W2051506593 cites W2003378104 @default.
• W2051506593 cites W2003836093 @default.
• W2051506593 cites W2008566738 @default.
• W2051506593 cites W2008921808 @default.
• W2051506593 cites W2015770897 @default.
• W2051506593 cites W2021268632 @default.
• W2051506593 cites W2022696619 @default.
• W2051506593 cites W2023271753 @default.
• W2051506593 cites W2023366100 @default.
• W2051506593 cites W2027408247 @default.
• W2051506593 cites W2028014186 @default.
• W2051506593 cites W2038486123 @default.
• W2051506593 cites W2041421251 @default.
• W2051506593 cites W2051088843 @default.
• W2051506593 cites W2052415011 @default.
• W2051506593 cites W2052468595 @default.
• W2051506593 cites W2055212608 @default.
• W2051506593 cites W2055725315 @default.
• W2051506593 cites W2057052341 @default.
• W2051506593 cites W2058606644 @default.
• W2051506593 cites W2059425402 @default.
• W2051506593 cites W2062637945 @default.
• W2051506593 cites W2063060974 @default.
• W2051506593 cites W2063210086 @default.
• W2051506593 cites W2068815231 @default.
• W2051506593 cites W2080249432 @default.
• W2051506593 cites W2082260955 @default.
• W2051506593 cites W2082867535 @default.
• W2051506593 cites W2086957099 @default.
• W2051506593 cites W2088113537 @default.
• W2051506593 cites W2090557687 @default.
• W2051506593 cites W2091049106 @default.
• W2051506593 cites W2091574192 @default.
• W2051506593 cites W2095797531 @default.
• W2051506593 cites W2102376488 @default.
• W2051506593 cites W2103731920 @default.
• W2051506593 cites W2106140689 @default.
• W2051506593 cites W2110043143 @default.
• W2051506593 cites W2110872379 @default.
• W2051506593 cites W2112154906 @default.
• W2051506593 cites W2113006529 @default.
• W2051506593 cites W2114814818 @default.
• W2051506593 cites W2116888257 @default.
• W2051506593 cites W2117518744 @default.
• W2051506593 cites W2119273654 @default.
• W2051506593 cites W2120901082 @default.
• W2051506593 cites W2123244946 @default.
• W2051506593 cites W2128312954 @default.
• W2051506593 cites W2132262459 @default.
• W2051506593 cites W2134713911 @default.
• W2051506593 cites W2135900956 @default.
• W2051506593 cites W2135974653 @default.
• W2051506593 cites W2141330782 @default.
• W2051506593 cites W2141838908 @default.
• W2051506593 cites W2142962510 @default.
• W2051506593 cites W2143981217 @default.
• W2051506593 cites W2144769216 @default.
• W2051506593 cites W2151124881 @default.
• W2051506593 cites W2151421295 @default.
• W2051506593 cites W2151430724 @default.
• W2051506593 cites W2152358306 @default.
• W2051506593 cites W2157107740 @default.
• W2051506593 cites W2159689520 @default.
• W2051506593 cites W2162166182 @default.
• W2051506593 cites W2162220273 @default.
• W2051506593 cites W2163306024 @default.
• W2051506593 cites W2169655552 @default.
• W2051506593 cites W2322008843 @default.

• next