Matches in SemOpenAlex for { <https://semopenalex.org/work/W2109686579> ?p ?o ?g. }
- W2109686579 endingPage "13" @default.
- W2109686579 startingPage "6" @default.
- W2109686579 abstract "Binding of Na(+) to thrombin ensures high activity toward physiological substrates and optimizes the procoagulant and prothrombotic roles of the enzyme in vivo. Under physiological conditions of pH and temperature, the binding affinity of Na(+) is weak due to large heat capacity and enthalpy changes associated with binding, and the K(d)=80 mM ensures only 64% saturation of the site at the concentration of Na(+) in the blood (140 mM). Residues controlling Na(+) binding and activation have been identified. Yet, attempts to improve the interaction of Na(+) with thrombin and possibly increase catalytic activity under physiological conditions have so far been unsuccessful. Here we report how replacement of the flexible autolysis loop of human thrombin with the homologous rigid domain of the murine enzyme results in a drastic (up to 10-fold) increase in Na(+) affinity and a significant improvement in the catalytic activity of the enzyme. Rigidification of the autolysis loop abolishes the heat capacity change associated with Na(+) binding observed in the wild-type and also increases the stability of thrombin. These findings have general relevance to protein engineering studies of clotting proteases and trypsin-like enzymes." @default.
- W2109686579 created "2016-06-24" @default.
- W2109686579 creator A5030972763 @default.
- W2109686579 creator A5046701540 @default.
- W2109686579 creator A5077357809 @default.
- W2109686579 creator A5086367121 @default.
- W2109686579 creator A5087503835 @default.
- W2109686579 date "2011-11-01" @default.
- W2109686579 modified "2023-09-25" @default.
- W2109686579 title "Rigidification of the autolysis loop enhances Na+ binding to thrombin" @default.
- W2109686579 cites W103344135 @default.
- W2109686579 cites W1520965512 @default.
- W2109686579 cites W1539796472 @default.
- W2109686579 cites W1772797489 @default.
- W2109686579 cites W1811402656 @default.
- W2109686579 cites W185683854 @default.
- W2109686579 cites W1945134141 @default.
- W2109686579 cites W1964944514 @default.
- W2109686579 cites W1968350868 @default.
- W2109686579 cites W1969786740 @default.
- W2109686579 cites W1969847251 @default.
- W2109686579 cites W1972112385 @default.
- W2109686579 cites W1972959684 @default.
- W2109686579 cites W1973212115 @default.
- W2109686579 cites W1976154028 @default.
- W2109686579 cites W1986260062 @default.
- W2109686579 cites W1986794972 @default.
- W2109686579 cites W1990004106 @default.
- W2109686579 cites W1994276989 @default.
- W2109686579 cites W1995070983 @default.
- W2109686579 cites W1996305694 @default.
- W2109686579 cites W1997255202 @default.
- W2109686579 cites W2001641653 @default.
- W2109686579 cites W2004021726 @default.
- W2109686579 cites W2004470519 @default.
- W2109686579 cites W2009460017 @default.
- W2109686579 cites W2013015862 @default.
- W2109686579 cites W2015906663 @default.
- W2109686579 cites W2017946980 @default.
- W2109686579 cites W2018281095 @default.
- W2109686579 cites W2021320002 @default.
- W2109686579 cites W2029428222 @default.
- W2109686579 cites W2029510213 @default.
- W2109686579 cites W2033684067 @default.
- W2109686579 cites W2035063408 @default.
- W2109686579 cites W2038670247 @default.
- W2109686579 cites W2038840577 @default.
- W2109686579 cites W2041814922 @default.
- W2109686579 cites W2046122729 @default.
- W2109686579 cites W2047192906 @default.
- W2109686579 cites W2049753237 @default.
- W2109686579 cites W2050392790 @default.
- W2109686579 cites W2051357919 @default.
- W2109686579 cites W2052066505 @default.
- W2109686579 cites W2052120397 @default.
- W2109686579 cites W2058252463 @default.
- W2109686579 cites W2059361463 @default.
- W2109686579 cites W2063342065 @default.
- W2109686579 cites W2067747440 @default.
- W2109686579 cites W2069023792 @default.
- W2109686579 cites W207453056 @default.
- W2109686579 cites W2074536184 @default.
- W2109686579 cites W2075593245 @default.
- W2109686579 cites W2076086429 @default.
- W2109686579 cites W2078528113 @default.
- W2109686579 cites W2079171916 @default.
- W2109686579 cites W2082841654 @default.
- W2109686579 cites W2083831568 @default.
- W2109686579 cites W2086179867 @default.
- W2109686579 cites W2087963628 @default.
- W2109686579 cites W2089553783 @default.
- W2109686579 cites W2092016944 @default.
- W2109686579 cites W2094323365 @default.
- W2109686579 cites W2109906659 @default.
- W2109686579 cites W2110399659 @default.
- W2109686579 cites W2112655878 @default.
- W2109686579 cites W2120712084 @default.
- W2109686579 cites W2123321071 @default.
- W2109686579 cites W2125324880 @default.
- W2109686579 cites W2129892556 @default.
- W2109686579 cites W2130166312 @default.
- W2109686579 cites W2132987695 @default.
- W2109686579 cites W2135735505 @default.
- W2109686579 cites W2138738787 @default.
- W2109686579 cites W2143986922 @default.
- W2109686579 cites W2144081223 @default.
- W2109686579 cites W2145166836 @default.
- W2109686579 cites W2148227359 @default.
- W2109686579 cites W2149610494 @default.
- W2109686579 cites W2151982987 @default.
- W2109686579 cites W2153975304 @default.
- W2109686579 cites W2157165549 @default.
- W2109686579 cites W2160439330 @default.
- W2109686579 cites W2161311348 @default.
- W2109686579 cites W2171229523 @default.
- W2109686579 cites W2395941632 @default.
- W2109686579 cites W2412820600 @default.
- W2109686579 cites W4211160326 @default.