{"entity": "journal", "iuid": "a68d853f393141c1b770ad9b772a05a0", "timestamp": "2026-08-26T22:47:01.902Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/journal/Int%20J%20Biol%20Macromol.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/journal/Int%20J%20Biol%20Macromol"}}, "title": "Int J Biol Macromol", "issn": "1879-0003", "issn-l": null, "publications_count": 5, "publications": [{"entity": "publication", "iuid": "5a3d2a140dcc4278a68afc3ab6fa0653", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5a3d2a140dcc4278a68afc3ab6fa0653.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5a3d2a140dcc4278a68afc3ab6fa0653"}}, "title": "Structural and antigen-binding surface definition of an anti-CD93 monoclonal antibody for the treatment of degenerative vascular eye diseases.", "authors": [{"family": "Raucci", "given": "Luisa", "initials": "L"}, {"family": "Perrone", "given": "Cosimo Damiano", "initials": "CD"}, {"family": "Barbera", "given": "Stefano", "initials": "S"}, {"family": "de Boer", "given": "Laurens Julius", "initials": "LJ"}, {"family": "Tosi", "given": "Gian Marco", "initials": "GM"}, {"family": "Brunetti", "given": "Jlenia", "initials": "J"}, {"family": "Bracci", "given": "Luisa", "initials": "L"}, {"family": "Pozzi", "given": "Cecilia", "initials": "C"}, {"family": "Galvagni", "given": "Federico", "initials": "F"}, {"family": "Orlandini", "given": "Maurizio", "initials": "M"}], "type": "journal article", "published": "2025-05-00", "journal": {"title": "Int J Biol Macromol", "issn": "1879-0003", "volume": "309", "issue": "Pt 4", "pages": "143118", "issn-l": null}, "abstract": "CD93 is a receptor predominantly expressed on the surface of endothelial cells, where it plays a pivotal role in angiogenesis through its interaction with the extracellular matrix. In our previous studies, we identified the monoclonal antibody 4E1 as a potent inhibitor of angiogenesis by targeting the CD93-Multimerin-2 axis. Here, we report the development of 4E1 as a recombinant whole immunoglobulin and a single-chain variable fragment, designated sc-4E. Both formats retained the binding properties of the parental monoclonal antibody and exhibited comparable inhibitory effects on endothelial cell migration and differentiation. To elucidate the molecular basis of the 4E1-CD93 interaction, we initially employed machine learning-based modeling and docking analyses of the variable heavy and light domains of 4E1. Subsequent crystallographic analysis of sc-4E provided high-resolution structural insights, confirming and validating the predicted model. Further docking experiments and molecular dynamics simulations using the crystallographic structures of CD93 and sc-4E revealed that the interaction is primarily mediated by the CDR-H3 and CDR-L2 loops. Notably, these regions engage with the sushi-like domain of CD93, which is critical for its interaction with Multimerin-2. This comprehensive structural and functional characterization of 4E1 and sc-4E underscores their potential as anti-angiogenic agents. By effectively inhibiting endothelial cell migration and differentiation, 4E1 derivatives represent promising therapeutic candidates for the treatment of ocular vascular diseases driven by pathological angiogenesis.", "doi": "10.1016/j.ijbiomac.2025.143118", "pmid": "40228767", "labels": [], "xrefs": [{"db": "pii", "key": "S0141-8130(25)03670-0"}], "notes": [], "created": "2026-08-21T11:20:34.015Z", "modified": "2026-08-21T11:20:34.030Z"}, {"entity": "publication", "iuid": "b51dd1abe8aa4142a88020b501e665ce", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b51dd1abe8aa4142a88020b501e665ce.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b51dd1abe8aa4142a88020b501e665ce"}}, "title": "Identification of a new Kir6 potassium channel and comparison of properties of Kir6 subtypes by structural modelling and molecular dynamics.", "authors": [{"family": "Criveanu", "given": "Dan", "initials": "D"}, {"family": "Bergqvist", "given": "Christina A", "initials": "CA"}, {"family": "Larhammar", "given": "Dan", "initials": "D"}, {"family": "Walczewska-Szewc", "given": "Katarzyna", "initials": "K"}], "type": "journal article", "published": "2023-08-30", "journal": {"title": "Int J Biol Macromol", "issn": "1879-0003", "volume": "247", "pages": "125771", "issn-l": null}, "abstract": "ATP-sensitive potassium ion channels (KATP) are transmembrane proteins that modulate insulin release and muscle contraction. KATP channels are composed of two types of subunit, Kir6 and SUR, which exist in two and three isoforms respectively with different tissue distribution. In this work, we identify a previously undescribed ancestral vertebrate gene encoding a Kir6-related protein that we have named Kir6.3, which may not have a SUR binding partner, unlike the other two Kir6 proteins. Whereas Kir6.3 was lost in amniotes including mammals, it is still present in several early-diverging vertebrate lineages such as frogs, coelacanth, and rayfinned fishes. Molecular dynamics (MD) simulations using homology models of Kir6.1, Kir6.2, and Kir6.3 from the coelacanth Latimeria chalumnae showed that the three proteins exhibit subtle differences in their dynamics. Steered MD simulations of Kir6-SUR pairs suggest that Kir6.3 has a lower binding affinity for the SUR proteins than either Kir6.1 or Kir6.2. As we found no additional SUR gene in the genomes of the species that have Kir6.3, it most likely forms a lone tetramer. These findings invite studies of the tissue distribution of Kir6.3 in relation to the other Kir6 as well as SUR proteins to determine the functional roles of Kir6.3.", "doi": "10.1016/j.ijbiomac.2023.125771", "pmid": "37433419", "labels": [], "xrefs": [{"db": "pii", "key": "S0141-8130(23)02665-X"}], "notes": [], "created": "2026-08-20T07:56:59.410Z", "modified": "2026-08-20T07:56:59.454Z"}, {"entity": "publication", "iuid": "47bbbaac2f43400e814855eedcd6d18a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/47bbbaac2f43400e814855eedcd6d18a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/47bbbaac2f43400e814855eedcd6d18a"}}, "title": "Dimerization of the C-type lectin-like receptor CD93 promotes its binding to Multimerin-2 in endothelial cells.", "authors": [{"family": "Barbera", "given": "Stefano", "initials": "S"}, {"family": "Raucci", "given": "Luisa", "initials": "L"}, {"family": "Tassone", "given": "Giusy", "initials": "G"}, {"family": "Tinti", "given": "Laura", "initials": "L"}, {"family": "Prischi", "given": "Filippo", "initials": "F"}, {"family": "Santucci", "given": "Annalisa", "initials": "A"}, {"family": "Mongiat", "given": "Maurizio", "initials": "M"}, {"family": "Tosi", "given": "Gian Marco", "initials": "GM"}, {"family": "Galvagni", "given": "Federico", "initials": "F"}, {"family": "Dimberg", "given": "Anna", "initials": "A"}, {"family": "Pozzi", "given": "Cecilia", "initials": "C"}, {"family": "Orlandini", "given": "Maurizio", "initials": "M"}], "type": "journal article", "published": "2023-01-01", "journal": {"title": "Int J Biol Macromol", "issn": "1879-0003", "volume": "224", "pages": "453-464", "issn-l": null}, "abstract": "Blocking the signaling activated by the plasma membrane receptor CD93 has recently been demonstrated a useful tool in antiangiogenic treatment and oncotherapy. In the proliferating endothelium, CD93 regulates cell adhesion, migration, and vascular maturation, yet it is unclear how CD93 interacts with the extracellular matrix activating signaling pathways involved in the vascular remodeling. Here for the first time we show that in endothelial cells CD93 is structured as a dimer and that this oligomeric form is physiologically instrumental for the binding of CD93 to its ligand Multimerin-2. Crystallographic X-ray analysis of recombinant CD93 reveals the crucial role played by the C-type lectin-like and sushi-like domains in arranging as an antiparallel dimer to achieve a functional binding state, providing key information for the future design of new drugs able to hamper CD93 function in neovascular pathologies.", "doi": "10.1016/j.ijbiomac.2022.10.136", "pmid": "36265539", "labels": [], "xrefs": [{"db": "pii", "key": "S0141-8130(22)02378-9"}], "notes": [], "created": "2026-08-20T07:56:57.198Z", "modified": "2026-08-20T07:56:57.268Z"}, {"entity": "publication", "iuid": "f4d8b78cca1b451b9b161ea5ca3fedc0", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f4d8b78cca1b451b9b161ea5ca3fedc0.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f4d8b78cca1b451b9b161ea5ca3fedc0"}}, "title": "Unravelling the mechanism of pH-regulation in dinoflagellate luciferase.", "authors": [{"family": "Kamerlin", "given": "Natasha", "initials": "N"}, {"family": "Delcey", "given": "Micka\u00ebl G", "initials": "MG"}, {"family": "Lindh", "given": "Roland", "initials": "R"}], "type": "journal article", "published": "2020-12-01", "journal": {"title": "Int J Biol Macromol", "issn": "1879-0003", "volume": "164", "pages": "2671-2680", "issn-l": null}, "abstract": "Dinoflagellates are the dominant source of bioluminescence in coastal waters. The luminescence reaction involves the oxidation of luciferin by a luciferase enzyme, which only takes place at low pH. The pH-dependence has previously been linked to four conserved histidines. It has been suggested that their protonation might induce a conformational change in the enzyme, thereby allowing substrate access to the binding pocket. Yet, the precise mechanism of luciferase activation has remained elusive. Here, we use computational tools to predict the open structure of the luciferase in Lingulodinium polyedra and to decipher the nature of the opening mechanism. Through accelerated molecular dynamics simulations, we demonstrate that the closed-open conformational change likely takes place via a tilt of the pH-regulatory helix-loop-helix domain. Moreover, we propose that the molecular basis for the transition is electrostatic repulsion between histidine-cation pairs, which destabilizes the closed conformation at low pH. Finally, by simulating truncated mutants, we show that eliminating the C-terminus alters the shape of the active site, effectively inactivating the luciferase.", "doi": "10.1016/j.ijbiomac.2020.08.071", "pmid": "32822730", "labels": [], "xrefs": [{"db": "pii", "key": "S0141-8130(20)34158-1"}], "notes": [], "created": "2026-08-21T11:20:32.000Z", "modified": "2026-08-21T11:20:32.013Z"}, {"entity": "publication", "iuid": "ce8e9ee921834289b5a6c6440cb84113", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ce8e9ee921834289b5a6c6440cb84113.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ce8e9ee921834289b5a6c6440cb84113"}}, "title": "Effect of a radiolabel biochemical nature on tumor-targeting properties of EpCAM-binding engineered scaffold protein DARPin Ec1.", "authors": [{"family": "Deyev", "given": "Sergey M", "initials": "SM"}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A"}, {"family": "Schulga", "given": "Alexey", "initials": "A"}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "G\u00fcnther", "given": "Tyran", "initials": "T"}, {"family": "Garousi", "given": "Javad", "initials": "J"}, {"family": "Konovalova", "given": "Elena", "initials": "E"}, {"family": "Ding", "given": "Haozhong", "initials": "H"}, {"family": "Gr\u00e4slund", "given": "Torbj\u00f6rn", "initials": "T"}, {"family": "Orlova", "given": "Anna", "initials": "A"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V"}], "type": "journal article", "published": "2020-02-15", "journal": {"title": "Int J Biol Macromol", "issn": "1879-0003", "volume": "145", "pages": "216-225", "issn-l": null}, "abstract": "Radionuclide-based imaging of molecular therapeutic targets might facilitate stratifying patients for specific biotherapeutics. New type of imaging probes, based on designed ankyrin repeat proteins (DARPins), have demonstrated excellent contrast of imaging of human epidermal growth factor type 2 (HER2) expression in preclinical models. We hypothesized that labeling approaches, which result in lipophilic radiometabolites (non-residualizing labels), would provide the best imaging contrast for DARPins that internalize slowly after binding to cancer cells. The hypothesis was tested using DARPin Ec1 that binds to epithelial cell adhesion molecule (EpCAM). EpCAM is a promising therapeutic target. Ec1 was labeled with 125I using two methods to obtain the non-residualizing labels, while residualizing labels were obtained by labeling it with 99mTc. All labeled Ec1 variants preserved target specificity and picomolar binding affinity to EpCAM-expressing pancreatic adenocarcinoma BxPC-3 cells. In murine models, all the variants provided similar tumor uptake. However, 125I-PIB-H6-Ec1 had noticeably lower retention in normal tissues, which provided appreciably higher tumor-to-organ ratios. Furthermore, 125I-PIB-H6-Ec1 demonstrated the highest imaging contrast in preclinical models than any other EpCAM-imaging agent tested so far. In conclusion, DARPin Ec1 in combination with a non-residualizing label is a promising probe for imaging EpCAM expression a few hours after injection.", "doi": "10.1016/j.ijbiomac.2019.12.147", "pmid": "31863835", "labels": [], "xrefs": [{"db": "pii", "key": "S0141-8130(19)39380-8"}], "notes": [], "created": "2026-08-21T11:20:30.050Z", "modified": "2026-08-21T11:20:30.082Z"}], "created": "2026-08-20T07:56:57.231Z", "modified": "2026-08-20T07:56:57.232Z"}