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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.<\/jats:p>","DOI":"10.1042\/bcj20220166","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T09:37:50Z","timestamp":1657013870000},"page":"1533-1542","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gain of function of a metalloproteinase associated with multiple myeloma, bicuspid aortic valve, and Von Hippel\u2013Lindau syndrome"],"prefix":"10.1042","volume":"479","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4239-6862","authenticated-orcid":false,"given":"Scott J.","family":"Snipas","sequence":"first","affiliation":[{"name":"1Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Jappelli","sequence":"additional","affiliation":[{"name":"1Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Torkamani","sequence":"additional","affiliation":[{"name":"2Scripps Research, La Jolla, CA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Paternostro","sequence":"additional","affiliation":[{"name":"1Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7933-6732","authenticated-orcid":false,"given":"Guy S.","family":"Salvesen","sequence":"additional","affiliation":[{"name":"1Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2022,7,21]]},"reference":[{"key":"2022072114354299100_BCJ-2022-0166C1","doi-asserted-by":"publisher","first-page":"6208","DOI":"10.3390\/ijms22126208","article-title":"Myeloma bone disease: a comprehensive review","volume":"22","year":"2021","journal-title":"Int. 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