Matches in SemOpenAlex for { <https://semopenalex.org/work/W2994748654> ?p ?o ?g. }
- W2994748654 endingPage "692" @default.
- W2994748654 startingPage "681" @default.
- W2994748654 abstract "Plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasminogen activators (PAs) tissue-type PA (tPA) and urokinase-type PA (uPA) plays a crucial role in many (patho)physiological processes (e.g., cardiovascular disease, tissue fibrosis) as well as in many age-related pathologies. Therefore, much effort has been put into the development of small molecule or antibody-based PAI-1 inhibitors.To elucidate the molecular mechanism of nanobody-induced PAI-1 inhibition.Here we present the first crystal structures of PAI-1 in complex with two neutralizing nanobodies (Nbs). These structures, together with biochemical and biophysical characterization, reveal that Nb VHH-2g-42 (Nb42) interferes with the initial PAI-1/PA complex formation, whereas VHH-2w-64 (Nb64) redirects the PAI-1/PA interaction to PAI-1 deactivation and regeneration of active PA. Furthermore, whereas vitronectin does not have an impact on the inhibitory effect of Nb42, it strongly potentiates the inhibitory effect of Nb64, which may contribute to a strong inhibitory potential of Nb64 in vivo.These findings illuminate the molecular mechanisms of PAI-1 inhibition. Nb42 and Nb64 can be used as starting points to engineer further improved antibody-based PAI-1 inhibitors or guide the rational design of small molecule inhibitors to treat a wide range of PAI-1-related pathophysiological conditions." @default.
- W2994748654 created "2019-12-26" @default.
- W2994748654 creator A5007438759 @default.
- W2994748654 creator A5018125023 @default.
- W2994748654 creator A5027251317 @default.
- W2994748654 creator A5061649794 @default.
- W2994748654 creator A5064777131 @default.
- W2994748654 creator A5068953187 @default.
- W2994748654 creator A5074388972 @default.
- W2994748654 creator A5087592855 @default.
- W2994748654 date "2020-03-01" @default.
- W2994748654 modified "2023-10-14" @default.
- W2994748654 title "Molecular mechanism of two nanobodies that inhibit PAI‐1 activity reveals a modulation at distinct stages of the PAI‐1/plasminogen activator interaction" @default.
- W2994748654 cites W1493779021 @default.
- W2994748654 cites W1547962072 @default.
- W2994748654 cites W1617233045 @default.
- W2994748654 cites W1753189859 @default.
- W2994748654 cites W1915197854 @default.
- W2994748654 cites W1934021954 @default.
- W2994748654 cites W1966370693 @default.
- W2994748654 cites W1969038776 @default.
- W2994748654 cites W1969608656 @default.
- W2994748654 cites W1970928930 @default.
- W2994748654 cites W1970939981 @default.
- W2994748654 cites W1971400041 @default.
- W2994748654 cites W1976057876 @default.
- W2994748654 cites W1976475852 @default.
- W2994748654 cites W1982730779 @default.
- W2994748654 cites W1983215505 @default.
- W2994748654 cites W1983498233 @default.
- W2994748654 cites W1988694095 @default.
- W2994748654 cites W1992648023 @default.
- W2994748654 cites W1993037158 @default.
- W2994748654 cites W1995196868 @default.
- W2994748654 cites W2002517434 @default.
- W2994748654 cites W2021246767 @default.
- W2994748654 cites W2031259785 @default.
- W2994748654 cites W2032615313 @default.
- W2994748654 cites W2035503835 @default.
- W2994748654 cites W2057358090 @default.
- W2994748654 cites W2060836090 @default.
- W2994748654 cites W2061346634 @default.
- W2994748654 cites W2062906571 @default.
- W2994748654 cites W2065420594 @default.
- W2994748654 cites W2065883241 @default.
- W2994748654 cites W2066088601 @default.
- W2994748654 cites W2069563497 @default.
- W2994748654 cites W2073900740 @default.
- W2994748654 cites W2077255131 @default.
- W2994748654 cites W2078142004 @default.
- W2994748654 cites W2090513179 @default.
- W2994748654 cites W2094126921 @default.
- W2994748654 cites W2106246537 @default.
- W2994748654 cites W2106554037 @default.
- W2994748654 cites W2118316826 @default.
- W2994748654 cites W2120776614 @default.
- W2994748654 cites W2130115771 @default.
- W2994748654 cites W2143660875 @default.
- W2994748654 cites W2151171807 @default.
- W2994748654 cites W2154197653 @default.
- W2994748654 cites W2163341755 @default.
- W2994748654 cites W2164591300 @default.
- W2994748654 cites W2167187823 @default.
- W2994748654 cites W2169610187 @default.
- W2994748654 cites W2170327826 @default.
- W2994748654 cites W2426848337 @default.
- W2994748654 cites W2517575661 @default.
- W2994748654 cites W2592958345 @default.
- W2994748654 cites W2616222401 @default.
- W2994748654 cites W2621285299 @default.
- W2994748654 cites W2751297798 @default.
- W2994748654 cites W2913613953 @default.
- W2994748654 doi "https://doi.org/10.1111/jth.14716" @default.
- W2994748654 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31858714" @default.
- W2994748654 hasPublicationYear "2020" @default.
- W2994748654 type Work @default.
- W2994748654 sameAs 2994748654 @default.
- W2994748654 citedByCount "10" @default.
- W2994748654 countsByYear W29947486542020 @default.
- W2994748654 countsByYear W29947486542021 @default.
- W2994748654 countsByYear W29947486542022 @default.
- W2994748654 countsByYear W29947486542023 @default.
- W2994748654 crossrefType "journal-article" @default.
- W2994748654 hasAuthorship W2994748654A5007438759 @default.
- W2994748654 hasAuthorship W2994748654A5018125023 @default.
- W2994748654 hasAuthorship W2994748654A5027251317 @default.
- W2994748654 hasAuthorship W2994748654A5061649794 @default.
- W2994748654 hasAuthorship W2994748654A5064777131 @default.
- W2994748654 hasAuthorship W2994748654A5068953187 @default.
- W2994748654 hasAuthorship W2994748654A5074388972 @default.
- W2994748654 hasAuthorship W2994748654A5087592855 @default.
- W2994748654 hasBestOaLocation W29947486541 @default.
- W2994748654 hasConcept C159654299 @default.
- W2994748654 hasConcept C161624437 @default.
- W2994748654 hasConcept C164144092 @default.
- W2994748654 hasConcept C169760540 @default.
- W2994748654 hasConcept C170493617 @default.
- W2994748654 hasConcept C17077164 @default.