{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lacham-Hartman S"],"funding":["United States - Israel Binational Science Foundation","Worldwide Cancer Research","European Research Council","Israel Science Foundation","NIGMS NIH HHS","Roberto and Cornelia Pallotti’s Legacy for Cancer Research"],"pagination":["e0249616"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8631645"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(11)"],"pubmed_abstract":["Although myriad protein-protein interactions in nature use polyvalent binding, in which multiple ligands on one entity bind to multiple receptors on another, to date an affinity advantage of polyvalent binding has been demonstrated experimentally only in cases where the target receptor molecules are clustered prior to complex formation. Here, we demonstrate cooperativity in binding affinity (i.e., avidity) for a protein complex in which an engineered dimer of the amyloid precursor protein inhibitor (APPI), possessing two fully functional inhibitory loops, interacts with mesotrypsin, a soluble monomeric protein that does not self-associate or cluster spontaneously. We found that each inhibitory loop of the purified APPI homodimer was over three-fold more potent than the corresponding loop i"],"journal":["PloS one"],"pubmed_title":["Avidity observed between a bivalent inhibitor and an enzyme monomer with a single active site."],"pmcid":["PMC8631645"],"funding_grant_id":["R01 GM144393","20-0238","875197","1004/20","2019303"],"pubmed_authors":["Shmidov Y","Radisky ES","Papo N","Lacham-Hartman S","Bitton R","Lukatsky DB"],"additional_accession":[]},"is_claimable":false,"name":"Avidity observed between a bivalent inhibitor and an enzyme monomer with a single active site.","description":"Although myriad protein-protein interactions in nature use polyvalent binding, in which multiple ligands on one entity bind to multiple receptors on another, to date an affinity advantage of polyvalent binding has been demonstrated experimentally only in cases where the target receptor molecules are clustered prior to complex formation. Here, we demonstrate cooperativity in binding affinity (i.e., avidity) for a protein complex in which an engineered dimer of the amyloid precursor protein inhibitor (APPI), possessing two fully functional inhibitory loops, interacts with mesotrypsin, a soluble monomeric protein that does not self-associate or cluster spontaneously. We found that each inhibitory loop of the purified APPI homodimer was over three-fold more potent than the corresponding loop i","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021","modification":"2026-05-08T23:47:23.586Z","creation":"2022-02-11T14:25:16.316Z"},"accession":"S-EPMC8631645","cross_references":{"pubmed":["34847142"],"doi":["10.1371/journal.pone.0249616"]}}