{"doi":"10.1042/bcj20220166","title":"Gain of function of a metalloproteinase associated with multiple myeloma, bicuspid aortic valve, and Von Hippel–Lindau syndrome","abstract":"A patient diagnosed with multiple myeloma, bicuspid aortic valve, and Von Hippel-Lindau syndrome underwent whole-exome sequencing seeking a unified genetic cause for these three pathologies. The patient possessed a single-point mutation of arginine to cysteine (R24C) in the N-terminal region(pro-domain) of matrix metalloproteinase 9 (MMP-9). The pro-domain interacts with the catalytic site of this enzyme rendering it inactive. MMP-9 has previously been associated with all three pathologies suffered by the patient. We hypothesized that the observed mutation in the pro-domain would influence the activity of this enzyme. We expressed recombinant versions of MMP-9 and an investigation of their biochemical properties revealed that MMP-9 R24C is a constitutively active zymogen. To our knowledge, this is the first example of a mutation that discloses catalytic activity in the pro-form in any of the 24 human MMPs.","journal":"Biochemical Journal","year":2022,"id":293817,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":978817,"name":"Roberto Jappelli","orcid":"0000-0002-0324-9085","position":1,"is_corresponding":false},{"id":27511,"name":"Ali Torkamani","orcid":"0000-0003-0232-8053","position":2,"is_corresponding":false},{"id":583091,"name":"Giovanni Paternostro","orcid":"0000-0003-4029-5467","position":3,"is_corresponding":false},{"id":90292,"name":"Guy S. Salvesen","orcid":"0000-0002-7933-6732","position":4,"is_corresponding":false},{"id":90282,"name":"Scott J. Snipas","orcid":"0000-0002-4239-6862","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T00:30:57.469517Z","pmid":"35789254","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}