FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308991631> ?p ?o ?g. }

• W4308991631 endingPage "1268" @default.
• W4308991631 startingPage "1258" @default.
• W4308991631 abstract "Platelet glycoprotein VI (GPVI) is attracting interest as a potential target for the development of new antiplatelet molecules with a low bleeding risk. GPVI binding to vascular collagen initiates thrombus formation and GPVI interactions with fibrin promote the growth and stability of the thrombus. In this study, we show that glenzocimab, a clinical stage humanized antibody fragment (Fab) with a high affinity for GPVI, blocks the binding of both ligands through a combination of steric hindrance and structural change. A cocrystal of glenzocimab with an extracellular domain of monomeric GPVI was obtained and its structure determined to a resolution of 1.9 Å. The data revealed that (1) glenzocimab binds to the D2 domain of GPVI, GPVI dimerization was not observed in the crystal structure because glenzocimab prevented D2 homotypic interactions and the formation of dimers that have a high affinity for collagen and fibrin; and (2) the light variable domain of the GPVI-bound Fab causes steric hindrance that is predicted to prevent the collagen-related peptide (CRP)/collagen fibers from extending out of their binding site and preclude GPVI clustering and downstream signaling. Glenzocimab did not bind to a truncated GPVI missing loop residues 129 to 136, thus validating the epitope identified in the crystal structure. Overall, these findings demonstrate that the binding of glenzocimab to the D2 domain of GPVI induces steric hindrance and structural modifications that drive the inhibition of GPVI interactions with its major ligands." @default.
• W4308991631 created "2022-11-20" @default.
• W4308991631 creator A5013189164 @default.
• W4308991631 creator A5013662355 @default.
• W4308991631 creator A5021733655 @default.
• W4308991631 creator A5027352248 @default.
• W4308991631 creator A5047676296 @default.
• W4308991631 creator A5051832282 @default.
• W4308991631 creator A5056684035 @default.
• W4308991631 creator A5057799772 @default.
• W4308991631 creator A5059289640 @default.
• W4308991631 creator A5061171100 @default.
• W4308991631 creator A5064624650 @default.
• W4308991631 creator A5071671948 @default.
• W4308991631 creator A5090170568 @default.
• W4308991631 date "2023-03-31" @default.
• W4308991631 modified "2023-10-02" @default.
• W4308991631 title "Targeting platelet GPVI with glenzocimab: a novel mechanism for inhibition" @default.
• W4308991631 cites W1517636809 @default.
• W4308991631 cites W17303524 @default.
• W4308991631 cites W1958827436 @default.
• W4308991631 cites W1972832497 @default.
• W4308991631 cites W1976679810 @default.
• W4308991631 cites W1999254278 @default.
• W4308991631 cites W2000336269 @default.
• W4308991631 cites W2013616695 @default.
• W4308991631 cites W2033262077 @default.
• W4308991631 cites W2061699884 @default.
• W4308991631 cites W2081919320 @default.
• W4308991631 cites W2090103763 @default.
• W4308991631 cites W2093722104 @default.
• W4308991631 cites W2104549677 @default.
• W4308991631 cites W2108921801 @default.
• W4308991631 cites W2110808180 @default.
• W4308991631 cites W2116621437 @default.
• W4308991631 cites W2124026197 @default.
• W4308991631 cites W2129958400 @default.
• W4308991631 cites W2130083671 @default.
• W4308991631 cites W2132629607 @default.
• W4308991631 cites W2144775786 @default.
• W4308991631 cites W2159211495 @default.
• W4308991631 cites W2163341755 @default.
• W4308991631 cites W2165122118 @default.
• W4308991631 cites W2165806239 @default.
• W4308991631 cites W2167626292 @default.
• W4308991631 cites W2212977094 @default.
• W4308991631 cites W2624156980 @default.
• W4308991631 cites W2782280176 @default.
• W4308991631 cites W2788305455 @default.
• W4308991631 cites W2789023287 @default.
• W4308991631 cites W2802703779 @default.
• W4308991631 cites W2940034580 @default.
• W4308991631 cites W2943936220 @default.
• W4308991631 cites W2962882716 @default.
• W4308991631 cites W2969713057 @default.
• W4308991631 cites W3033364143 @default.
• W4308991631 cites W3042854765 @default.
• W4308991631 cites W3044275663 @default.
• W4308991631 cites W3109251586 @default.
• W4308991631 cites W3122889567 @default.
• W4308991631 cites W3123826032 @default.
• W4308991631 cites W3130169871 @default.
• W4308991631 cites W3164412598 @default.
• W4308991631 cites W4220889580 @default.
• W4308991631 cites W4248872320 @default.
• W4308991631 cites W4280630871 @default.
• W4308991631 doi "https://doi.org/10.1182/bloodadvances.2022007863" @default.
• W4308991631 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36375047" @default.
• W4308991631 hasPublicationYear "2023" @default.
• W4308991631 type Work @default.
• W4308991631 citedByCount "8" @default.
• W4308991631 countsByYear W43089916312023 @default.
• W4308991631 crossrefType "journal-article" @default.
• W4308991631 hasAuthorship W4308991631A5013189164 @default.
• W4308991631 hasAuthorship W4308991631A5013662355 @default.
• W4308991631 hasAuthorship W4308991631A5021733655 @default.
• W4308991631 hasAuthorship W4308991631A5027352248 @default.
• W4308991631 hasAuthorship W4308991631A5047676296 @default.
• W4308991631 hasAuthorship W4308991631A5051832282 @default.
• W4308991631 hasAuthorship W4308991631A5056684035 @default.
• W4308991631 hasAuthorship W4308991631A5057799772 @default.
• W4308991631 hasAuthorship W4308991631A5059289640 @default.
• W4308991631 hasAuthorship W4308991631A5061171100 @default.
• W4308991631 hasAuthorship W4308991631A5064624650 @default.
• W4308991631 hasAuthorship W4308991631A5071671948 @default.
• W4308991631 hasAuthorship W4308991631A5090170568 @default.
• W4308991631 hasBestOaLocation W43089916311 @default.
• W4308991631 hasConcept C107824862 @default.
• W4308991631 hasConcept C108625454 @default.
• W4308991631 hasConcept C12554922 @default.
• W4308991631 hasConcept C126322002 @default.
• W4308991631 hasConcept C166014724 @default.
• W4308991631 hasConcept C170493617 @default.
• W4308991631 hasConcept C185592680 @default.
• W4308991631 hasConcept C195687474 @default.
• W4308991631 hasConcept C201194858 @default.
• W4308991631 hasConcept C203014093 @default.
• W4308991631 hasConcept C26828662 @default.

• next