{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T21:54:35Z","timestamp":1794347675001,"version":"4.9.0"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2001,12,21]],"date-time":"2001-12-21T00:00:00Z","timestamp":1008892800000},"content-version":"vor","delay-in-days":203,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2001,6]]},"abstract":"<jats:p>The plasminogen activator, surface protease Pla, of the plague bacterium <jats:italic>Yersinia pestis<\/jats:italic> is an important virulence factor that enables the spread of <jats:italic>Y. pestis<\/jats:italic> from subcutaneous sites into circulation. Pla\u2010expressing <jats:italic>Y. pestis<\/jats:italic> and recombinant <jats:italic>Escherichia coli<\/jats:italic> formed active plasmin in the presence of the major human plasmin inhibitor, \u03b1<jats:sub>2<\/jats:sub>\u2010antiplasmin, and the bacteria were found to inactivate \u03b1<jats:sub>2<\/jats:sub>\u2010antiplasmin. In contrast, only poor plasminogen activation and no cleavage of \u03b1<jats:sub>2<\/jats:sub>\u2010antiplasmin was observed with recombinant bacteria expressing the homologous gene <jats:italic>ompT<\/jats:italic> from <jats:italic>E. coli<\/jats:italic>. A \u03b2\u2010barrel topology model for Pla and OmpT predicted 10 transmembrane \u03b2\u2010strands and five surface\u2010exposed loops L1\u2013L5. Hybrid Pla\u2013OmpT proteins were created by substituting each of the loops between Pla and OmpT. Analysis of the hybrid molecules suggested a critical role of L3 and L4 in the substrate specificity of Pla towards plasminogen and \u03b1<jats:sub>2<\/jats:sub>\u2010antiplasmin. Substitution analysis at 25 surface\u2010located residues showed the importance of the conserved residues H101, H208, D84, D86, D206 and S99 for the proteolytic activity of Pla\u2010expressing recombinant <jats:italic>E. coli<\/jats:italic>. The mature \u03b1\u2010Pla of 292 amino acids was processed into \u03b2\u2010Pla by an autoprocessing cleavage at residue K262, and residues important for the self\u2010recognition of Pla were identified. Prevention of autoprocessing of Pla, however, had no detectable effect on plasminogen activation or cleavage of \u03b1<jats:sub>2<\/jats:sub>\u2010antiplasmin. Cleavage of \u03b1<jats:sub>2<\/jats:sub>\u2010antiplasmin and plasminogen activation were influenced by residue R211 in L4 as well as by unidentified residues in L3. OmpT, which is not associated with invasive bacterial disease, was converted into a Pla\u2010like protease by deleting residues D214 and P215, by substituting residue K217 for R217 in L4 of OmpT and also by substituting the entire L3 with that from Pla. This simple modification of the surface loops and the substrate specificity of OmpT exemplifies the evolution of a housekeeping protein into a virulence factor by subtle mutations at critical protein regions. We propose that inactivation of \u03b1<jats:sub>2<\/jats:sub>\u2010antiplasmin by Pla of <jats:italic>Y. pestis<\/jats:italic> promotes uncontrolled proteolysis and contributes to the invasive character of plague.<\/jats:p>","DOI":"10.1046\/j.1365-2958.2001.02451.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T11:38:01Z","timestamp":1047469081000},"page":"1097-1111","source":"Crossref","is-referenced-by-count":106,"title":["Protein regions important for plasminogen activation and inactivation of \u03b1<sub>2<\/sub>\u2010antiplasmin in the surface protease Pla of <i>Yersinia pestis<\/i>"],"prefix":"10.1111","volume":"40","author":[{"given":"Maini","family":"Kukkonen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaarina","family":"L\u00e4hteenm\u00e4ki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo","family":"Suomalainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisse","family":"Kalkkinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levente","family":"Em\u00f6dy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannu","family":"L\u00e5ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo K.","family":"Korhonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,12,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.24.14043"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.94.1.19-26.1967"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02605861"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1111\/j.1365-2958.1991.tb00790.x","article-title":"Type 1 fimbriae mutants of Escherichia coli K\u201012: characterization of recognized afimbriate strains and construction of new fim deletion mutants","volume":"5","author":"Blomfield I.C.","year":"1991","journal-title":"Mol Microbiol"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-65297-4_4"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.149.3682.422"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3838593"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1997.2871652.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.31.2.839-841.1981"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1994.tb01279.x"},{"key":"e_1_2_6_12_1","first-page":"99","article-title":"Studies on the pathogenesis of plague: blood coagulation and tissue responses of Macaca mulatta following exposure to aerosols of Pasteurella pestis","volume":"53","author":"Finegold M.J.","year":"1968","journal-title":"Am J Pathol"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2000.0989"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.170.3.1245-1253.1988"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.3.1209"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.14.4077-4086.2000"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.15.7351"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1086\/314456"},{"key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4049\/jimmunol.49.1.15","article-title":"Studies on plague immunity in experimental animals II. 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