FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2164112820> ?p ?o ?g. }

• W2164112820 endingPage "1464" @default.
• W2164112820 startingPage "1457" @default.
• W2164112820 abstract "Although Thr is equally represented as Ser in the human genome and as a nucleophile is as good as Ser, it is never found in the active site of the large family of trypsin-like proteases that utilize the Asp/His/Ser triad. The molecular basis of the preference of Ser over Thr in the trypsin fold was investigated with X-ray structures of the thrombin mutant S195T free and bound to an irreversible active site inhibitor. In the free form, the methyl group of T195 is oriented toward the incoming substrate in a conformation seemingly incompatible with productive binding. In the bound form, the side chain of T195 is reoriented for efficient substrate acylation without causing steric clash within the active site. Rapid kinetics prove that this change is due to selection of an active conformation from a preexisting ensemble of reactive and unreactive rotamers whose relative distribution determines the level of activity of the protease. Consistent with these observations, the S195T substitution is associated with a weak yet finite activity that allows identification of an unanticipated important role for S195 as the end point of allosteric transduction in the trypsin fold. The S195T mutation abrogates the Na+-dependent enhancement of catalytic activity in thrombin, activated protein C, and factor Xa and significantly weakens the physiologically important allosteric effects of thrombomodulin on thrombin and of cofactor Va on factor Xa. The evolutionary selection of Ser over Thr in trypsin-like proteases was therefore driven by the need for high catalytic activity and efficient allosteric regulation." @default.
• W2164112820 created "2016-06-24" @default.
• W2164112820 creator A5013522961 @default.
• W2164112820 creator A5013803228 @default.
• W2164112820 creator A5046701540 @default.
• W2164112820 creator A5071486914 @default.
• W2164112820 creator A5077357809 @default.
• W2164112820 creator A5087503835 @default.
• W2164112820 date "2015-02-11" @default.
• W2164112820 modified "2023-10-16" @default.
• W2164112820 title "Why Ser and Not Thr Brokers Catalysis in the Trypsin Fold" @default.
• W2164112820 cites W121755589 @default.
• W2164112820 cites W1525517607 @default.
• W2164112820 cites W1539796472 @default.
• W2164112820 cites W17569331 @default.
• W2164112820 cites W1964439982 @default.
• W2164112820 cites W1967860838 @default.
• W2164112820 cites W1969324434 @default.
• W2164112820 cites W1969847251 @default.
• W2164112820 cites W1976951969 @default.
• W2164112820 cites W1977832025 @default.
• W2164112820 cites W1977881358 @default.
• W2164112820 cites W1979263745 @default.
• W2164112820 cites W1982354968 @default.
• W2164112820 cites W1984541502 @default.
• W2164112820 cites W1985031469 @default.
• W2164112820 cites W1989992559 @default.
• W2164112820 cites W1997255202 @default.
• W2164112820 cites W1999859798 @default.
• W2164112820 cites W2001641653 @default.
• W2164112820 cites W2003801270 @default.
• W2164112820 cites W2004091546 @default.
• W2164112820 cites W2004789938 @default.
• W2164112820 cites W2005280179 @default.
• W2164112820 cites W2023297908 @default.
• W2164112820 cites W2024641847 @default.
• W2164112820 cites W2027345286 @default.
• W2164112820 cites W2037592320 @default.
• W2164112820 cites W2047225916 @default.
• W2164112820 cites W2048822589 @default.
• W2164112820 cites W2050072584 @default.
• W2164112820 cites W2056894234 @default.
• W2164112820 cites W2062819748 @default.
• W2164112820 cites W2064964147 @default.
• W2164112820 cites W2072174642 @default.
• W2164112820 cites W2079598721 @default.
• W2164112820 cites W2080359163 @default.
• W2164112820 cites W2084190685 @default.
• W2164112820 cites W2086179867 @default.
• W2164112820 cites W2087381350 @default.
• W2164112820 cites W2091748192 @default.
• W2164112820 cites W2094079380 @default.
• W2164112820 cites W2101572186 @default.
• W2164112820 cites W2102990316 @default.
• W2164112820 cites W2107542943 @default.
• W2164112820 cites W2109906659 @default.
• W2164112820 cites W2110975370 @default.
• W2164112820 cites W2121897924 @default.
• W2164112820 cites W2122976061 @default.
• W2164112820 cites W2132412188 @default.
• W2164112820 cites W2135735505 @default.
• W2164112820 cites W2141919103 @default.
• W2164112820 cites W2142423474 @default.
• W2164112820 cites W2144081223 @default.
• W2164112820 cites W2146890570 @default.
• W2164112820 cites W2148101168 @default.
• W2164112820 cites W2149610494 @default.
• W2164112820 cites W2151746312 @default.
• W2164112820 cites W2152997175 @default.
• W2164112820 cites W2156289248 @default.
• W2164112820 cites W2157165549 @default.
• W2164112820 cites W2160439330 @default.
• W2164112820 cites W2161311348 @default.
• W2164112820 cites W2170055916 @default.
• W2164112820 cites W2180229411 @default.
• W2164112820 cites W2323630730 @default.
• W2164112820 cites W2401430279 @default.
• W2164112820 cites W2885134480 @default.
• W2164112820 cites W4211160326 @default.
• W2164112820 cites W4246995357 @default.
• W2164112820 cites W4251174927 @default.
• W2164112820 cites W92618250 @default.
• W2164112820 doi "https://doi.org/10.1021/acs.biochem.5b00014" @default.
• W2164112820 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4342846" @default.
• W2164112820 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25664608" @default.
• W2164112820 hasPublicationYear "2015" @default.
• W2164112820 type Work @default.
• W2164112820 sameAs 2164112820 @default.
• W2164112820 citedByCount "12" @default.
• W2164112820 countsByYear W21641128202015 @default.
• W2164112820 countsByYear W21641128202016 @default.
• W2164112820 countsByYear W21641128202019 @default.
• W2164112820 countsByYear W21641128202020 @default.
• W2164112820 countsByYear W21641128202021 @default.
• W2164112820 countsByYear W21641128202022 @default.
• W2164112820 crossrefType "journal-article" @default.
• W2164112820 hasAuthorship W2164112820A5013522961 @default.
• W2164112820 hasAuthorship W2164112820A5013803228 @default.

• next