{"entity": "researcher", "timestamp": "2026-07-12T08:30:07.813Z", "family": "Khakzad", "given": "Hamed", "initials": "H", "orcid": "0000-0002-8556-0650", "affiliations": ["Equipe Signalisation Calcique et Infections Microbiennes , Ecole Normale Sup\u00e9rieure Paris-Saclay , 91190 Gif-sur-Yvette , France.", "Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1282 , 91190 Gif-sur-Yvette , France."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/a7b030c1452c4dc9b430deffdf493e6f.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/a7b030c1452c4dc9b430deffdf493e6f"}}, "publications": [{"entity": "publication", "iuid": "be1ccad457054a6ca82002c69b0dacdb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/be1ccad457054a6ca82002c69b0dacdb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/be1ccad457054a6ca82002c69b0dacdb"}}, "title": "Streptolysin O accelerates the conversion of plasminogen to plasmin", "authors": [{"family": "Tang", "given": "Di", "initials": "D", "orcid": "0000-0001-6323-9375", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2a27467c4094d9f8d8f8402efa333f4.json"}}, {"family": "Khakzad", "given": "Hamed", "initials": "H", "orcid": "0000-0002-8556-0650", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7b030c1452c4dc9b430deffdf493e6f.json"}}, {"family": "Hjortswang", "given": "Elisabeth", "initials": "E"}, {"family": "Malmstr\u00f6m", "given": "Lars", "initials": "L", "orcid": "0000-0001-9885-9312", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e99f34fb854beb8d810b05fe941057.json"}}, {"family": "Ekstr\u00f6m", "given": "Simon", "initials": "S", "orcid": "0000-0002-7694-285X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6416b323664f4126b70067193d7b8347.json"}}, {"family": "Happonen", "given": "Lotta", "initials": "L", "orcid": "0000-0002-5922-4549", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7af0a6faf6a48e7937a644be472edbe.json"}}, {"family": "Malmstr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0002-2889-7169", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad3c999da10c41e4a3afda2718815083.json"}}], "type": "journal-article", "published": "2024-11-25", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "15", "issue": "1", "pages": "10212"}, "abstract": "Group A Streptococcus (GAS) is a human-specific bacterial pathogen that can exploit the plasminogen-plasmin fibrinolysis system to dismantle blood clots and facilitate its spread and survival within the human host. In this study, we use affinity-enrichment mass spectrometry to decipher the host-pathogen protein-protein interaction between plasminogen and streptolysin O, a key cytolytic toxin produced by GAS. This interaction accelerates the conversion of plasminogen to plasmin by both the host tissue-type plasminogen activator and streptokinase, a bacterial plasminogen activator secreted by GAS. Integrative structural mass spectrometry analysis shows that the interaction induces local conformational shifts in plasminogen. These changes lead to the formation of a stabilised intermediate plasminogen-streptolysin O complex that becomes significantly more susceptible to proteolytic processing by plasminogen activators. Our findings reveal a conserved and moonlighting pathomechanistic function for streptolysin O that extends beyond its well-characterised cytolytic activity.", "doi": "10.1038/s41467-024-54173-6", "pmid": "39587097", "labels": {"Structural Proteomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-024-54173-6"}, {"db": "pmc", "key": "PMC11589678"}], "notes": [], "created": "2024-11-27T17:20:53.877Z", "modified": "2024-11-28T17:40:23.904Z"}, {"entity": "publication", "iuid": "b2a30a6011bb47659582e0b4cdce2803", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b2a30a6011bb47659582e0b4cdce2803.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b2a30a6011bb47659582e0b4cdce2803"}}, "title": "The hinge-engineered IgG1-IgG3 hybrid subclass IgGh47 potently enhances Fc-mediated function of anti-streptococcal and SARS-CoV-2 antibodies.", "authors": [{"family": "Izadi", "given": "Arman", "initials": "A", "orcid": "0000-0002-0262-1017", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d6f1927cfc643818a0a3a1b8602af14.json"}}, {"family": "Karami", "given": "Yasaman", "initials": "Y", "orcid": "0000-0001-8413-2665", "researcher": {"href": "https://publications.scilifelab.se/researcher/a71f08b3f3794e66b7adae400c14f142.json"}}, {"family": "Bratanis", "given": "Eleni", "initials": "E", "orcid": "0000-0002-0636-6658", "researcher": {"href": "https://publications.scilifelab.se/researcher/c935953f81fc4d8eb6a9b9ddb7774c1b.json"}}, {"family": "Wrighton", "given": "Sebastian", "initials": "S", "orcid": "0000-0002-3378-7925", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b5821cc01364325a4b9fe177e7f6e33.json"}}, {"family": "Khakzad", "given": "Hamed", "initials": "H", "orcid": "0000-0002-8556-0650", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7b030c1452c4dc9b430deffdf493e6f.json"}}, {"family": "Nyblom", "given": "Maria", "initials": "M"}, {"family": "Olofsson", "given": "Berit", "initials": "B", "orcid": "0009-0009-0602-2183", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ad483473b044b7dbc7e6c61ef1c0a73.json"}}, {"family": "Happonen", "given": "Lotta", "initials": "L", "orcid": "0000-0002-5922-4549", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7af0a6faf6a48e7937a644be472edbe.json"}}, {"family": "Tang", "given": "Di", "initials": "D", "orcid": "0000-0001-6323-9375", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2a27467c4094d9f8d8f8402efa333f4.json"}}, {"family": "Sundwall", "given": "Martin", "initials": "M", "orcid": "0000-0002-0114-6613", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc0080c10aa64cd7b073813c8ebc0bc7.json"}}, {"family": "Godzwon", "given": "Magdalena", "initials": "M"}, {"family": "Chao", "given": "Yashuan", "initials": "Y", "orcid": "0000-0002-0295-3142", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed7bd7c821754977ba516c3e1c04eceb.json"}}, {"family": "Toledo", "given": "Alejandro Gomez", "initials": "AG", "orcid": "0000-0002-2103-7158", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e9d9a5e2dc148c9bcdc07f2b4a17ebc.json"}}, {"family": "Schmidt", "given": "Tobias", "initials": "T", "orcid": "0000-0001-9943-4121", "researcher": {"href": "https://publications.scilifelab.se/researcher/2eba2593dde24540a7d70aa3b593e4fc.json"}}, {"family": "Ohlin", "given": "Mats", "initials": "M", "orcid": "0000-0002-5105-1938", "researcher": {"href": "https://publications.scilifelab.se/researcher/fda1d1ed0b074a04a69b0c8b036dd001.json"}}, {"family": "Nilges", "given": "Michael", "initials": "M", "orcid": "0000-0002-1451-8092", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebfd5336137d4eaabde8f4f9baed470a.json"}}, {"family": "Malmstr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0002-2889-7169", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad3c999da10c41e4a3afda2718815083.json"}}, {"family": "Bahnan", "given": "Wael", "initials": "W"}, {"family": "Shannon", "given": "Oonagh", "initials": "O", "orcid": "0000-0001-8291-8189", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed4685bab7584028a070fc5a829bd386.json"}}, {"family": "Malmstr\u00f6m", "given": "Lars", "initials": "L", "orcid": "0000-0001-9885-9312", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e99f34fb854beb8d810b05fe941057.json"}}, {"family": "Nordenfelt", "given": "Pontus", "initials": "P", "orcid": "0000-0002-9481-9951", "researcher": {"href": "https://publications.scilifelab.se/researcher/7aa3418ab23a4ec48c037d6d6ddea5b5.json"}}], "type": "journal article", "published": "2024-04-27", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "3600", "issn-l": "2041-1723"}, "abstract": "Streptococcus pyogenes can cause invasive disease with high mortality despite adequate antibiotic treatments. To address this unmet need, we have previously generated an opsonic IgG1 monoclonal antibody, Ab25, targeting the bacterial M protein. Here, we engineer the IgG2-4 subclasses of Ab25. Despite having reduced binding, the IgG3 version promotes stronger phagocytosis of bacteria. Using atomic simulations, we show that IgG3's Fc tail has extensive movement in 3D space due to its extended hinge region, possibly facilitating interactions with immune cells. We replaced the hinge of IgG1 with four different IgG3-hinge segment subclasses, IgGhxx. Hinge-engineering does not diminish binding as with IgG3 but enhances opsonic function, where a 47 amino acid hinge is comparable to IgG3 in function. IgGh47 shows improved protection against S. pyogenes in a systemic infection mouse model, suggesting that IgGh47 has promise as a preclinical therapeutic candidate. Importantly, the enhanced opsonic function of IgGh47 is generalizable to diverse S. pyogenes strains from clinical isolates. We generated IgGh47 versions of anti-SARS-CoV-2 mAbs to broaden the biological applicability, and these also exhibit strongly enhanced opsonic function compared to the IgG1 subclass. The improved function of the IgGh47 subclass in two distant biological systems provides new insights into antibody function.", "doi": "10.1038/s41467-024-47928-8", "pmid": "38678029", "labels": {"Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11055898"}, {"db": "pii", "key": "10.1038/s41467-024-47928-8"}], "notes": [], "created": "2024-11-08T09:49:22.468Z", "modified": "2025-10-17T13:05:07.370Z"}, {"entity": "publication", "iuid": "6e75301d789743ad907f297d66dc7bee", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6e75301d789743ad907f297d66dc7bee.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6e75301d789743ad907f297d66dc7bee"}}, "title": "Multienzyme deep learning models improve peptide de novo sequencing by mass spectrometry proteomics.", "authors": [{"family": "Gueto-Tettay", "given": "Carlos", "initials": "C", "orcid": "0000-0002-8496-6341", "researcher": {"href": "https://publications.scilifelab.se/researcher/b0e4a5377a88414588686e5630b0be66.json"}}, {"family": "Tang", "given": "Di", "initials": "D", "orcid": "0000-0001-6323-9375", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2a27467c4094d9f8d8f8402efa333f4.json"}}, {"family": "Happonen", "given": "Lotta", "initials": "L"}, {"family": "Heusel", "given": "Moritz", "initials": "M", "orcid": "0000-0002-8506-530X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c404e5fdd701412093882c1e48d0bc93.json"}}, {"family": "Khakzad", "given": "Hamed", "initials": "H", "orcid": "0000-0002-8556-0650", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7b030c1452c4dc9b430deffdf493e6f.json"}}, {"family": "Malmstr\u00f6m", "given": "Johan", "initials": "J"}, {"family": "Malmstr\u00f6m", "given": "Lars", "initials": "L", "orcid": "0000-0001-9885-9312", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e99f34fb854beb8d810b05fe941057.json"}}], "type": "journal article", "published": "2023-01-00", "journal": {"title": "PLoS Comput. Biol.", "issn": "1553-7358", "volume": "19", "issue": "1", "pages": "e1010457", "issn-l": "1553-734X"}, "abstract": "Generating and analyzing overlapping peptides through multienzymatic digestion is an efficient procedure for de novo protein using from bottom-up mass spectrometry (MS). Despite improved instrumentation and software, de novo MS data analysis remains challenging. In recent years, deep learning models have represented a performance breakthrough. Incorporating that technology into de novo protein sequencing workflows require machine-learning models capable of handling highly diverse MS data. In this study, we analyzed the requirements for assembling such generalizable deep learning models by systemcally varying the composition and size of the training set. We assessed the generated models' performances using two test sets composed of peptides originating from the multienzyme digestion of samples from various species. The peptide recall values on the test sets showed that the deep learning models generated from a collection of highly N- and C-termini diverse peptides generalized 76% more over the termini-restricted ones. Moreover, expanding the training set's size by adding peptides from the multienzymatic digestion with five proteases of several species samples led to a 2-3 fold generalizability gain. Furthermore, we tested the applicability of these multienzyme deep learning (MEM) models by fully de novo sequencing the heavy and light monomeric chains of five commercial antibodies (mAbs). MEMs extracted over 10000 matching and overlapped peptides across six different proteases mAb samples, achieving a 100% sequence coverage for 8 of the ten polypeptide chains. We foretell that the MEMs' proven improvements to de novo analysis will positively impact several applications, such as analyzing samples of high complexity, unknown nature, or the peptidomics field.", "doi": "10.1371/journal.pcbi.1010457", "pmid": "36668672", "labels": {"Structural Proteomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC9891523"}, {"db": "pii", "key": "PCOMPBIOL-D-22-01182"}], "notes": [], "created": "2023-05-31T19:03:01.330Z", "modified": "2023-05-31T19:03:36.693Z"}, {"entity": "publication", "iuid": "58bd18b8aa7c4321abc5d8460a21059b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/58bd18b8aa7c4321abc5d8460a21059b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/58bd18b8aa7c4321abc5d8460a21059b"}}, "title": "The structure of human dermatan sulfate epimerase 1 emphasizes the importance of C5-epimerization of glucuronic acid in higher organisms.", "authors": [{"family": "Hasan", "given": "Mahmudul", "initials": "M", "orcid": "0000-0002-1767-6440", "researcher": {"href": "https://publications.scilifelab.se/researcher/67859983152248efb9f5a0461b168273.json"}}, {"family": "Khakzad", "given": "Hamed", "initials": "H", "orcid": "0000-0002-8556-0650", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7b030c1452c4dc9b430deffdf493e6f.json"}}, {"family": "Happonen", "given": "Lotta", "initials": "L", "orcid": "0000-0002-5922-4549", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7af0a6faf6a48e7937a644be472edbe.json"}}, {"family": "Sundin", "given": "Anders", "initials": "A", "orcid": "0000-0001-6615-2419", "researcher": {"href": "https://publications.scilifelab.se/researcher/b03a78e59f0845c5b68b372f2709dbf0.json"}}, {"family": "Unge", "given": "Johan", "initials": "J", "orcid": "0000-0002-1077-8137", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3aa8d0b4eaf489b8b35e825bb522ca0.json"}}, {"family": "Mueller", "given": "Uwe", "initials": "U", "orcid": "0000-0002-7139-0718", "researcher": {"href": "https://publications.scilifelab.se/researcher/0dec0ec0f53448d19f40b384e727daff.json"}}, {"family": "Malmstr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0002-2889-7169", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad3c999da10c41e4a3afda2718815083.json"}}, {"family": "Westergren-Thorsson", "given": "Gunilla", "initials": "G", "orcid": "0000-0001-5327-8805", "researcher": {"href": "https://publications.scilifelab.se/researcher/08bbfee41c5545779fa88211baeeb216.json"}}, {"family": "Malmstr\u00f6m", "given": "Lars", "initials": "L", "orcid": "0000-0001-9885-9312", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e99f34fb854beb8d810b05fe941057.json"}}, {"family": "Ellervik", "given": "Ulf", "initials": "U", "orcid": "0000-0001-5287-0137", "researcher": {"href": "https://publications.scilifelab.se/researcher/079345b11c884e25ae5f968b70eb9d13.json"}}, {"family": "Malmstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0002-6691-146X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c756d46971f4670abdb5faafb10ad56.json"}}, {"family": "Tykesson", "given": "Emil", "initials": "E", "orcid": "0000-0002-0511-9831", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd615245d50b47639f38f55fbf3f4fe3.json"}}], "type": "journal article", "published": "2021-02-07", "journal": {"title": "Chem. Sci.", "issn": "2041-6520", "volume": "12", "issue": "5", "pages": "1869-1885", "issn-l": null}, "abstract": "Dermatan sulfate epimerase 1 (DS-epi1, EC 5.1.3.19) catalyzes the conversion of d-glucuronic acid to l-iduronic acid on the polymer level, a key step in the biosynthesis of the glycosaminoglycan dermatan sulfate. Here, we present the first crystal structure of the catalytic domains of DS-epi1, solved at 2.4 \u00c5 resolution, as well as a model of the full-length luminal protein obtained by a combination of macromolecular crystallography and targeted cross-linking mass spectrometry. Based on docking studies and molecular dynamics simulations of the protein structure and a chondroitin substrate, we suggest a novel mechanism of DS-epi1, involving a His/double-Tyr motif. Our work uncovers detailed information about the domain architecture, active site, metal-coordinating center and pattern of N-glycosylation of the protein. Additionally, the structure of DS-epi1 reveals a high structural similarity to proteins from several families of bacterial polysaccharide lyases. DS-epi1 is of great importance in a range of diseases, and the structure provides a necessary starting point for design of active site inhibitors.", "doi": "10.1039/d0sc05971d", "pmid": "33815739", "labels": {"Structural Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "d0sc05971d"}, {"db": "pmc", "key": "PMC8006597"}], "notes": [], "created": "2021-12-03T12:29:01.165Z", "modified": "2021-12-03T12:29:01.545Z"}, {"entity": "publication", "iuid": "03a9bb0f8fa14a829220610e1ac822c4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/03a9bb0f8fa14a829220610e1ac822c4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/03a9bb0f8fa14a829220610e1ac822c4"}}, "title": "Structural determination of Streptococcus pyogenes M1 protein interactions with human immunoglobulin G using integrative structural biology.", "authors": [{"family": "Khakzad", "given": "Hamed", "initials": "H", "orcid": "0000-0002-8556-0650", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7b030c1452c4dc9b430deffdf493e6f.json"}}, {"family": "Happonen", "given": "Lotta", "initials": "L", "orcid": "0000-0002-5922-4549", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7af0a6faf6a48e7937a644be472edbe.json"}}, {"family": "Karami", "given": "Yasaman", "initials": "Y", "orcid": "0000-0001-8413-2665", "researcher": {"href": "https://publications.scilifelab.se/researcher/a71f08b3f3794e66b7adae400c14f142.json"}}, {"family": "Chowdhury", "given": "Sounak", "initials": "S"}, {"family": "Bergdahl", "given": "Gizem Ert\u00fcrk", "initials": "GE", "orcid": "0000-0001-9719-6609", "researcher": {"href": "https://publications.scilifelab.se/researcher/f3671f82049b4e8e96fd45b0e0351642.json"}}, {"family": "Nilges", "given": "Michael", "initials": "M", "orcid": "0000-0002-1451-8092", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebfd5336137d4eaabde8f4f9baed470a.json"}}, {"family": "Tran Van Nhieu", "given": "Guy", "initials": "G"}, {"family": "Malmstr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0002-2889-7169", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad3c999da10c41e4a3afda2718815083.json"}}, {"family": "Malmstr\u00f6m", "given": "Lars", "initials": "L", "orcid": "0000-0001-9885-9312", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e99f34fb854beb8d810b05fe941057.json"}}], "type": "journal article", "published": "2021-01-00", "journal": {"title": "PLoS Comput. Biol.", "issn": "1553-7358", "volume": "17", "issue": "1", "pages": "e1008169", "issn-l": "1553-734X"}, "abstract": "Streptococcus pyogenes (Group A streptococcus; GAS) is an important human pathogen responsible for mild to severe, life-threatening infections. GAS expresses a wide range of virulence factors, including the M family proteins. The M proteins allow the bacteria to evade parts of the human immune defenses by triggering the formation of a dense coat of plasma proteins surrounding the bacteria, including IgGs. However, the molecular level details of the M1-IgG interaction have remained unclear. Here, we characterized the structure and dynamics of this interaction interface in human plasma on the surface of live bacteria using integrative structural biology, combining cross-linking mass spectrometry and molecular dynamics (MD) simulations. We show that the primary interaction is formed between the S-domain of M1 and the conserved IgG Fc-domain. In addition, we show evidence for a so far uncharacterized interaction between the A-domain and the IgG Fc-domain. Both these interactions mimic the protein G-IgG interface of group C and G streptococcus. These findings underline a conserved scavenging mechanism used by GAS surface proteins that block the IgG-receptor (Fc\u03b3R) to inhibit phagocytic killing. We additionally show that we can capture Fab-bound IgGs in a complex background and identify XLs between the constant region of the Fab-domain and certain regions of the M1 protein engaged in the Fab-mediated binding. Our results elucidate the M1-IgG interaction network involved in inhibition of phagocytosis and reveal important M1 peptides that can be further investigated as future vaccine targets.", "doi": "10.1371/journal.pcbi.1008169", "pmid": "33411763", "labels": {"Structural Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "PCOMPBIOL-D-20-01263"}, {"db": "pmc", "key": "PMC7817036"}], "notes": [], "created": "2021-12-03T12:29:48.339Z", "modified": "2021-12-03T12:29:48.505Z"}]}