{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:42:12Z","timestamp":1792759332097,"version":"4.5.0"},"reference-count":52,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association Inc","doi-asserted-by":"publisher","award":["25POST1372745"],"award-info":[{"award-number":["25POST1372745"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["R35HL171421"],"award-info":[{"award-number":["R35HL171421"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013449","name":"American Society for Horticultural Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001422","name":"American Society of Hematology Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001422","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jthjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Thrombosis and Haemostasis"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.jtha.2026.09.003","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:32:24Z","timestamp":1788910344000},"update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mapping the mutational landscape for streptokinase binding to plasminogen"],"prefix":"10.1016","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8371-3588","authenticated-orcid":false,"given":"Srishti","family":"Baid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3477-3012","authenticated-orcid":false,"given":"Matthew L.","family":"Holding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8596-0317","authenticated-orcid":false,"given":"Taylor","family":"Laurin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Siemieniak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6436-8942","authenticated-orcid":false,"given":"David","family":"Ginsburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-659X","authenticated-orcid":false,"given":"Laura M.","family":"Haynes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jtha.2026.09.003_bib1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0027502","article-title":"Borrelia burgdorferi enolase is a surface-exposed plasminogen binding protein","volume":"6","author":"Floden","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.jtha.2026.09.003_bib2","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0968-0004(99)01521-2","article-title":"Molecular mechanisms of plasminogen activation: bacterial cofactors provide clues","volume":"25","author":"Parry","year":"2000","journal-title":"Trends Biochem Sci"},{"key":"10.1016\/j.jtha.2026.09.003_bib3","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1126\/science.1101245","article-title":"Plasminogen is a critical host pathogenicity factor for group A streptococcal infection","volume":"305","author":"Sun","year":"2004","journal-title":"Science"},{"key":"10.1016\/j.jtha.2026.09.003_bib4","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-96710-z","article-title":"Whole genome sequencing reveals possible host species adaptation of Streptococcus dysgalactiae","volume":"11","author":"Porcellato","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.jtha.2026.09.003_bib5","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/s41579-023-00865-7","article-title":"Pathogenesis, epidemiology and control of Group A Streptococcus infection","volume":"21","author":"Brouwer","year":"2023","journal-title":"Nat Rev Microbiol"},{"key":"10.1016\/j.jtha.2026.09.003_bib6","article-title":"The burden of group A Streptococcus (GAS) infections: the challenge continues in the twenty-first century","volume":"28","author":"Thacharodi","year":"2024","journal-title":"iScience"},{"key":"10.1016\/j.jtha.2026.09.003_bib7","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/9509604","article-title":"Pathogenicity of virulent species of Group C Streptococci in human","volume":"2017","author":"K\u0142os","year":"2017","journal-title":"Can J Infect Dis Med Microbiol"},{"key":"10.1016\/j.jtha.2026.09.003_bib8","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.02578-24","article-title":"Integrative genomic, virulence, and transcriptomic analysis of emergent Streptococcus dysgalactiae subspecies equisimilis (SDSE) emm type stG62647 isolates causing human infections","volume":"15","author":"Eraso","year":"2024","journal-title":"mBio"},{"key":"10.1016\/j.jtha.2026.09.003_bib9","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1111\/mmi.12037","article-title":"Streptokinase variants from Streptococcus pyogenes isolates display altered plasminogen activation characteristics - implications for pathogenesis","volume":"86","author":"Cook","year":"2012","journal-title":"Mol Microbiol"},{"key":"10.1016\/j.jtha.2026.09.003_bib10","series-title":"Stroke. Pathophysiology, diagnosis, and management","first-page":"13","article-title":"Mechanisms of thrombosis and thrombolysis","author":"del Zoppo","year":"2015"},{"key":"10.1016\/j.jtha.2026.09.003_bib11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1042\/BJ20131305","article-title":"Site-restricted plasminogen activation mediated by group A streptococcal streptokinase variants","volume":"458","author":"Cook","year":"2014","journal-title":"Biochem J"},{"key":"10.1016\/j.jtha.2026.09.003_bib12","doi-asserted-by":"crossref","first-page":"12609","DOI":"10.1074\/jbc.M009265200","article-title":"The mechanism of a bacterial plasminogen activator intermediate between streptokinase and staphylokinase","volume":"276","author":"Sazonova","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.09.003_bib13","doi-asserted-by":"crossref","first-page":"14579","DOI":"10.1074\/jbc.275.19.14579","article-title":"Streptokinase binds to human plasmin with high affinity, perturbs the plasmin active site, and induces expression of a substrate recognition exosite for plasminogen","volume":"275","author":"Boxrud","year":"2000","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.09.003_bib52","doi-asserted-by":"crossref","first-page":"29482","DOI":"10.1074\/jbc.M113.477935","article-title":"Full time course kinetics of the streptokinase-plasminogen activation pathway","volume":"288","author":"Nolan","year":"2013","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.09.003_bib14","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/j.1365-2958.1989.tb01808.x","article-title":"The streptokinase gene of group A streptococci: cloning, expression in Escherichia coli, and sequence analysis","volume":"3","author":"Huang","year":"1989","journal-title":"Mol Microbiol"},{"key":"10.1016\/j.jtha.2026.09.003_bib15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11239-006-9011-x","article-title":"Streptokinase--the drug of choice for thrombolytic therapy","volume":"23","author":"Kunamneni","year":"2007","journal-title":"J Thromb Thrombolysis"},{"key":"10.1016\/j.jtha.2026.09.003_bib16","doi-asserted-by":"crossref","first-page":"218","DOI":"10.2174\/187152571103140120103816","article-title":"Towards a superior streptokinase for fibrinolytic therapy of vascular thrombosis","volume":"11","author":"Keramati","year":"2013","journal-title":"Cardiovasc Hematol Agents Med Chem"},{"key":"10.1016\/j.jtha.2026.09.003_bib17","article-title":"A systematic review of the efficacy and safety of tenecteplase versus streptokinase in the management of myocardial infarction in developing countries","volume":"15","author":"Muoghalu","year":"2023","journal-title":"Cureus"},{"key":"10.1016\/j.jtha.2026.09.003_bib18","doi-asserted-by":"crossref","first-page":"265S","DOI":"10.1378\/chest.95.5.265S","article-title":"Comparison of tissue plasminogen activator and streptokinase in the management of acute myocardial infarction","volume":"95","author":"White","year":"1989","journal-title":"Chest"},{"key":"10.1016\/j.jtha.2026.09.003_bib19","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1002\/pro.5560071017","article-title":"Analysis of the interactions between streptokinase domains and human plasminogen","volume":"7","author":"Conejero-Lara","year":"1998","journal-title":"Protein Sci"},{"key":"10.1016\/j.jtha.2026.09.003_bib20","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1126\/science.281.5383.1662","article-title":"Crystal structure of the catalytic domain of human plasmin complexed with streptokinase","volume":"281","author":"Wang","year":"1998","journal-title":"Science"},{"key":"10.1016\/j.jtha.2026.09.003_bib21","doi-asserted-by":"crossref","first-page":"S106","DOI":"10.1111\/jth.12939","article-title":"Pathogen activators of plasminogen","volume":"13","author":"Verhamme","year":"2015","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.09.003_bib22","doi-asserted-by":"crossref","first-page":"26084","DOI":"10.1074\/jbc.M101966200","article-title":"Streptokinase triggers conformational activation of plasminogen through specific interactions of the amino-terminal sequence and stabilizes the active zymogen conformation","volume":"276","author":"Boxrud","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.09.003_bib23","doi-asserted-by":"crossref","first-page":"14686","DOI":"10.1021\/bi011309d","article-title":"Domain interactions between streptokinase and human plasminogen","volume":"40","author":"Loy","year":"2001","journal-title":"Biochemistry"},{"key":"10.1016\/j.jtha.2026.09.003_bib24","doi-asserted-by":"crossref","DOI":"10.1074\/jbc.RA120.016262","article-title":"Streptococcus co-opts a conformational lock in human plasminogen to facilitate streptokinase cleavage and bacterial virulence","volume":"296","author":"Ayinuola","year":"2021","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.09.003_bib25","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.csbj.2019.06.023","article-title":"Structural biology and protein engineering of thrombolytics","volume":"17","author":"Mican","year":"2019","journal-title":"Comput Struct Biotechnol J"},{"key":"10.1016\/j.jtha.2026.09.003_bib26","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-97871-7","article-title":"Deep mutational scanning of the plasminogen activator inhibitor-1 functional landscape","volume":"11","author":"Huttinger","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.jtha.2026.09.003_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2022.102608","article-title":"Deep mutational scanning and massively parallel kinetics of plasminogen activator inhibitor-1 functional stability to probe its latency transition","volume":"298","author":"Haynes","year":"2022","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.09.003_bib28","doi-asserted-by":"crossref","DOI":"10.1002\/pro.70088","article-title":"High-throughput amino acid-level characterization of the interactions of plasminogen activator inhibitor-1 with variably divergent proteases","volume":"34","author":"Haynes","year":"2025","journal-title":"Protein Sci"},{"key":"10.1016\/j.jtha.2026.09.003_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2025.110896","article-title":"Thermodynamics and selection of the plasminogen activator inhibitor-1 latency transition","volume":"301","author":"Haynes","year":"2025","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.09.003_bib30","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ab.2011.04.025","article-title":"Engineering streptokinase for generation of active site-labeled plasminogen analogs","volume":"415","author":"Laha","year":"2011","journal-title":"Anal Biochem"},{"key":"10.1016\/j.jtha.2026.09.003_bib31","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1111\/jth.12629","article-title":"Biosimilars: the process is the product. The example of recombinant streptokinase","volume":"12","author":"Thelwell","year":"2014","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.09.003_bib32","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.jtha.2026.09.003_bib33","doi-asserted-by":"crossref","first-page":"7504","DOI":"10.1074\/jbc.M411637200","article-title":"Role of the streptokinase alpha-domain in the interactions of streptokinase with plasminogen and plasmin","volume":"280","author":"Bean","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.09.003_bib34","doi-asserted-by":"crossref","first-page":"24421","DOI":"10.1074\/jbc.M301825200","article-title":"Structure-function analysis of the streptokinase amino terminus (residues 1-59)","volume":"278","author":"Mundada","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.09.003_bib35","doi-asserted-by":"crossref","first-page":"13257","DOI":"10.1074\/jbc.M108422200","article-title":"Involvement of a nine-residue loop of streptokinase in the generation of macromolecular substrate specificity by the activator complex through interaction with substrate kringle domains","volume":"277","author":"Dhar","year":"2002","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.09.003_bib36","doi-asserted-by":"crossref","first-page":"19511","DOI":"10.1074\/jbc.M109.005512","article-title":"Plasminogen substrate recognition by the streptokinase-plasminogen catalytic complex is facilitated by Arg253, Lys256, and Lys257 in the streptokinase beta-domain and kringle 5 of the substrate","volume":"284","author":"Tharp","year":"2009","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.09.003_bib37","doi-asserted-by":"crossref","first-page":"26774","DOI":"10.1074\/jbc.C600171200","article-title":"Binding of the COOH-terminal lysine residue of streptokinase to plasmin(ogen) kringles enhances formation of the streptokinase.plasmin(ogen) catalytic complexes","volume":"281","author":"Panizzi","year":"2006","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.09.003_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.rpth.2025.102874","article-title":"Halo fluorescence fibrinolysis test: a novel quantitative assay to evaluate fibrinolysis on established plasma clots","volume":"9","author":"Liu","year":"2025","journal-title":"Res Pract Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.09.003_bib39","doi-asserted-by":"crossref","DOI":"10.1002\/rth2.12771","article-title":"A novel ex vivo approach for measuring plasminogen activation upon established plasma clots","volume":"6","author":"Palazzolo","year":"2022","journal-title":"Res Pract Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.09.003_bib40","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0049-3848(88)90218-6","article-title":"Activation of Val442-plasminogen (mini-plasminogen) by urokinase, streptokinase and tissue plasminogen activator","volume":"49","author":"Takada","year":"1988","journal-title":"Thromb Res"},{"key":"10.1016\/j.jtha.2026.09.003_bib41","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1093\/bioinformatics\/btz740","article-title":"EvoEF2: accurate and fast energy function for computational protein design","volume":"36","author":"Huang","year":"2020","journal-title":"Bioinformatics"},{"key":"10.1016\/j.jtha.2026.09.003_bib42","doi-asserted-by":"crossref","first-page":"W382","DOI":"10.1093\/nar\/gki387","article-title":"The FoldX web server: an online force field","volume":"33","author":"Schymkowitz","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jtha.2026.09.003_bib43","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1093\/molbev\/msp146","article-title":"Structural determinants of protein evolution are context-sensitive at the residue level","volume":"26","author":"Franzosa","year":"2009","journal-title":"Mol Biol Evol"},{"key":"10.1016\/j.jtha.2026.09.003_bib44","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2025.116446","article-title":"Multi-environment deep mutational scanning reveals the distribution of temperature-sensitive variants in a bacterial kinase","volume":"44","author":"Ghose","year":"2025","journal-title":"Cell Rep"},{"key":"10.1016\/j.jtha.2026.09.003_bib45","doi-asserted-by":"crossref","DOI":"10.1126\/science.adq3948","article-title":"Genetics, energetics, and allostery in proteins with randomized cores and surfaces","volume":"389","author":"Escobedo","year":"2025","journal-title":"Science"},{"key":"10.1016\/j.jtha.2026.09.003_bib46","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.tim.2006.01.006","article-title":"Phage display in the study of infectious diseases","volume":"14","author":"Mullen","year":"2006","journal-title":"Trends Microbiol"},{"key":"10.1016\/j.jtha.2026.09.003_bib47","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/17425255.2024.2311168","article-title":"Comparison of pharmacokinetic properties of alteplase and tenecteplase. The future of thrombolysis in acute ischemic stroke","volume":"20","author":"Mar\u00e8","year":"2024","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"10.1016\/j.jtha.2026.09.003_bib48","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"10.1016\/j.jtha.2026.09.003_bib49","doi-asserted-by":"crossref","first-page":"D364","DOI":"10.1093\/nar\/gku1028","article-title":"A series of PDB-related databanks for everyday needs","volume":"43","author":"Touw","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jtha.2026.09.003_bib50","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0080635","article-title":"Maximum allowed solvent accessibilites of residues in proteins","volume":"8","author":"Tien","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.jtha.2026.09.003_bib51","doi-asserted-by":"crossref","DOI":"10.1093\/molbev\/msaf290","article-title":"Tandem duplication of serpin genes yields functional variation and snake venom inhibitors","volume":"42","author":"Ward","year":"2025","journal-title":"Mol Biol Evol"}],"container-title":["Journal of Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783626005635?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783626005635?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T11:56:20Z","timestamp":1792756580000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1538783626005635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":52,"alternative-id":["S1538783626005635"],"URL":"https:\/\/doi.org\/10.1016\/j.jtha.2026.09.003","relation":{},"ISSN":["1538-7836"],"issn-type":[{"value":"1538-7836","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mapping the mutational landscape for streptokinase binding to plasminogen","name":"articletitle","label":"Article Title"},{"value":"Journal of Thrombosis and Haemostasis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jtha.2026.09.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Inc. on behalf of International Society on Thrombosis and Haemostasis.","name":"copyright","label":"Copyright"}]}}