| http://purl.uniprot.org/citations/36257932 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36257932 | http://www.w3.org/2000/01/rdf-schema#comment | "The metzincin metalloproteinase PAPP-A plays a key role in the regulation of insulin-like growth factor (IGF) signaling by specific cleavage of inhibitory IGF binding proteins (IGFBPs). Using single-particle cryo-electron microscopy (cryo-EM), we here report the structure of PAPP-A in complex with its endogenous inhibitor, stanniocalcin-2 (STC2), neither of which have been reported before. The highest resolution (3.1 Å) was obtained for the STC2 subunit and the N-terminal approximately 1000 residues of the PAPP-A subunit. The 500 kDa 2:2 PAPP-A·STC2 complex is a flexible multidomain ensemble with numerous interdomain contacts. In particular, a specific disulfide bond between the subunits of STC2 and PAPP-A prevents dissociation, and interactions between STC2 and a module located in the very C-terminal end of the PAPP-A subunit prevent binding of its main substrate, IGFBP-4. While devoid of activity towards IGFBP-4, the active site cleft of the catalytic domain is accessible in the inhibited PAPP-A·STC2 complex, as shown by its ability to hydrolyze a synthetic peptide derived from IGFBP-4. Relevant to multiple human pathologies, this unusual mechanism of proteolytic inhibition may support the development of specific pharmaceutical agents, by which IGF signaling can be indirectly modulated."xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41467-022-33698-8"xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://purl.uniprot.org/core/author | "Gajhede M."xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://purl.uniprot.org/core/author | "Boesen T."xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://purl.uniprot.org/core/author | "Oxvig C."xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://purl.uniprot.org/core/author | "Kloverpris S."xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://purl.uniprot.org/core/author | "Mikkelsen J.H."xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://purl.uniprot.org/core/author | "Kjaer T.R."xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://purl.uniprot.org/core/author | "Kobbero S.D."xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://purl.uniprot.org/core/author | "Mirza O.A."xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/36257932 | http://purl.uniprot.org/core/name | "Nat Commun"xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://purl.uniprot.org/core/pages | "6084"xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://purl.uniprot.org/core/title | "Structure of the proteolytic enzyme PAPP-A with the endogenous inhibitor stanniocalcin-2 reveals its inhibitory mechanism."xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://purl.uniprot.org/core/volume | "13"xsd:string |
| http://purl.uniprot.org/citations/36257932 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/36257932 |
| http://purl.uniprot.org/citations/36257932 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/36257932 |
| http://purl.uniprot.org/uniprot/#_Q13219-mappedCitation-36257932 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36257932 |
| http://purl.uniprot.org/uniprot/#_O76061-mappedCitation-36257932 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36257932 |
| http://purl.uniprot.org/uniprot/Q13219 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/36257932 |
| http://purl.uniprot.org/uniprot/O76061 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/36257932 |