Matches in SemOpenAlex for { <https://semopenalex.org/work/W2141087890> ?p ?o ?g. }
- W2141087890 endingPage "308" @default.
- W2141087890 startingPage "297" @default.
- W2141087890 abstract "Abstract A congeneric series of four bis‐benzamidine inhibitors sharing a dianhydrosugar isosorbide scaffold in common has been studied by crystal structure analysis and enzyme kinetics with respect to their binding to trypsin and factor Xa. Within the series, aromatic interactions are an important determinant for selectivity discrimination among both serine proteases. To study the selectivity‐determining features in detail, we used trypsin mutants in which the original binding site is gradually substituted to finally resemble the factor Xa binding pocket. The influence of these mutations has been analyzed on the binding of the closely related inhibitors. We present the crystal structures of the inhibitor complexes obtained by co‐crystallizing an “intermediate” trypsin mutant. They could be determined to a resolution of up to 1.2 Å, and we measured the inhibitory activity ( K i ) of each ligand against factor Xa, trypsin, and the various mutants. From these data we were able to derive a detailed structure–activity relationship which demonstrates the importance of aromatic interactions in protein–ligand recognition and their role in modulating enzyme selectivity. Pronounced preference is experienced to accommodate the benzamidine anchor with meta topology in the S 1 specificity pocket. One ligand possessing only para topology deviates strongly from the other members of the series and adopts a distinct binding mode addressing the S 1 ′ site instead of the distal S 3 /S 4 binding pocket." @default.
- W2141087890 created "2016-06-24" @default.
- W2141087890 creator A5001025464 @default.
- W2141087890 creator A5005420915 @default.
- W2141087890 creator A5051157923 @default.
- W2141087890 creator A5085961742 @default.
- W2141087890 date "2007-03-01" @default.
- W2141087890 modified "2023-10-18" @default.
- W2141087890 title "Understanding Binding Selectivity toward Trypsin and Factor Xa: the Role of Aromatic Interactions" @default.
- W2141087890 cites W104793819 @default.
- W2141087890 cites W1539796472 @default.
- W2141087890 cites W1568609060 @default.
- W2141087890 cites W1864506204 @default.
- W2141087890 cites W1964069747 @default.
- W2141087890 cites W1966842782 @default.
- W2141087890 cites W1969885133 @default.
- W2141087890 cites W1972363382 @default.
- W2141087890 cites W1973950081 @default.
- W2141087890 cites W1981750741 @default.
- W2141087890 cites W1984444278 @default.
- W2141087890 cites W1986191025 @default.
- W2141087890 cites W1987006301 @default.
- W2141087890 cites W1988771765 @default.
- W2141087890 cites W1993672505 @default.
- W2141087890 cites W1995017064 @default.
- W2141087890 cites W2001641653 @default.
- W2141087890 cites W2003035408 @default.
- W2141087890 cites W2003356525 @default.
- W2141087890 cites W2005191262 @default.
- W2141087890 cites W2007236469 @default.
- W2141087890 cites W2007763197 @default.
- W2141087890 cites W2009104988 @default.
- W2141087890 cites W2013083986 @default.
- W2141087890 cites W2020034925 @default.
- W2141087890 cites W2020620545 @default.
- W2141087890 cites W2022476928 @default.
- W2141087890 cites W2025524908 @default.
- W2141087890 cites W2026395206 @default.
- W2141087890 cites W2027773741 @default.
- W2141087890 cites W2034503332 @default.
- W2141087890 cites W2045787836 @default.
- W2141087890 cites W2046634819 @default.
- W2141087890 cites W2047241264 @default.
- W2141087890 cites W2048631643 @default.
- W2141087890 cites W2052039776 @default.
- W2141087890 cites W2054525948 @default.
- W2141087890 cites W2054582528 @default.
- W2141087890 cites W2058099725 @default.
- W2141087890 cites W2062714484 @default.
- W2141087890 cites W2063831812 @default.
- W2141087890 cites W2064729826 @default.
- W2141087890 cites W2066942802 @default.
- W2141087890 cites W2068447247 @default.
- W2141087890 cites W2071467721 @default.
- W2141087890 cites W2076071870 @default.
- W2141087890 cites W2076533072 @default.
- W2141087890 cites W2079604571 @default.
- W2141087890 cites W2080476827 @default.
- W2141087890 cites W2080594183 @default.
- W2141087890 cites W2092826347 @default.
- W2141087890 cites W2094186244 @default.
- W2141087890 cites W2095168548 @default.
- W2141087890 cites W2097123790 @default.
- W2141087890 cites W2098099612 @default.
- W2141087890 cites W2107439114 @default.
- W2141087890 cites W2108508060 @default.
- W2141087890 cites W2111687291 @default.
- W2141087890 cites W2118587156 @default.
- W2141087890 cites W2119112311 @default.
- W2141087890 cites W2122995887 @default.
- W2141087890 cites W2123321071 @default.
- W2141087890 cites W2136144807 @default.
- W2141087890 cites W2146217734 @default.
- W2141087890 cites W2163407325 @default.
- W2141087890 cites W2166386419 @default.
- W2141087890 cites W2410661499 @default.
- W2141087890 cites W2950724979 @default.
- W2141087890 cites W4231412904 @default.
- W2141087890 cites W4234608381 @default.
- W2141087890 cites W4242881867 @default.
- W2141087890 cites W4255886946 @default.
- W2141087890 doi "https://doi.org/10.1002/cmdc.200600185" @default.
- W2141087890 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17191291" @default.
- W2141087890 hasPublicationYear "2007" @default.
- W2141087890 type Work @default.
- W2141087890 sameAs 2141087890 @default.
- W2141087890 citedByCount "28" @default.
- W2141087890 countsByYear W21410878902012 @default.
- W2141087890 countsByYear W21410878902013 @default.
- W2141087890 countsByYear W21410878902014 @default.
- W2141087890 countsByYear W21410878902015 @default.
- W2141087890 countsByYear W21410878902016 @default.
- W2141087890 countsByYear W21410878902018 @default.
- W2141087890 countsByYear W21410878902019 @default.
- W2141087890 countsByYear W21410878902022 @default.
- W2141087890 countsByYear W21410878902023 @default.
- W2141087890 crossrefType "journal-article" @default.
- W2141087890 hasAuthorship W2141087890A5001025464 @default.