{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:06:53Z","timestamp":1789495613575,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001658","name":"Minerva Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001658","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004410","name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ft\u0131rma Kurumu","doi-asserted-by":"publisher","award":["119F392"],"award-info":[{"award-number":["119F392"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Transition metals (e.g., Fe\n                    <jats:sup>2\/3+<\/jats:sup>\n                    , Zn\n                    <jats:sup>2+<\/jats:sup>\n                    , Mn\n                    <jats:sup>2+<\/jats:sup>\n                    ) are essential enzymatic cofactors in all organisms. Their environmental scarcity led to the evolution of high\u2010affinity uptake systems. Our research focuses on two bacterial manganese ABC importers,\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    PsaBC and\n                    <jats:italic>Bacillus anthracis<\/jats:italic>\n                    MntBC, both critical for virulence. Both importers share a similar homodimeric structure, where each protomer comprises a transmembrane domain (TMD) linked to a cytoplasmic nucleotide\u2010binding domain (NBD). Due to their size and slow turnover rates, the utility of conventional molecular simulation approaches to reveal functional dynamics is limited. Thus, we employed a novel, computationally efficient method integrating Gaussian Network Models (GNM) with information theory Transfer Entropy (TE) calculations. Our calculations are in remarkable agreement with previous functional studies. Furthermore, based on the calculations, we generated 10 point\u2010mutations and experimentally tested their effects, finding excellent concordance between computational predictions and experimental results. We identified \u201callosteric hotspots\u201d in both transporters, in the transmembrane translocation pathway, at the coupling helices linking the TMDs and NBDs, and in the ATP binding sites. In both PsaBC and MntBC, we observed bi\u2010directional information flow between the two TMDs, with minimal allosteric transmission to the NBDs. Conversely, the NBDs exhibited almost no NBD\u2010NBD allosteric crosstalk but showed pronounced information flow from the NBD of one protomer towards the TMD of the other protomer. This unique allosteric \u201cfootprint\u201d distinguishes ABC importers of transition metals from other members of the ABC transporter superfamily establishing them as a distinct functional class. This study offers the first comprehensive insight into the conformational dynamics of these vital virulence determinants, providing potential avenues for developing urgently needed novel antibacterial agents.\n                  <\/jats:p>","DOI":"10.1002\/pro.70039","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T01:30:26Z","timestamp":1738200626000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Computational and experimental mapping of the allosteric network of two manganese\n                    <scp>ABC<\/scp>\n                    transporters"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4985-3712","authenticated-orcid":false,"given":"Ozge","family":"Duman","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering Bogazici University  Istanbul Turkey"},{"name":"Polymer Research Center Bogazici University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiya","family":"Kuznetsova","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology Bruce and Ruth Rappaport Faculty of Medicine, Technion\u2010Israel Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurit Livnat","family":"Levanon","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology Bruce and Ruth Rappaport Faculty of Medicine, Technion\u2010Israel Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moti","family":"Grupper","sequence":"additional","affiliation":[{"name":"Infectious Disease Unit Rambam Health Care Campus  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akarun Ayca","family":"Ersoy","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Bogazici University  Istanbul Turkey"},{"name":"Polymer Research Center Bogazici University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burcin","family":"Acar","sequence":"additional","affiliation":[{"name":"Polymer Research Center Bogazici University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0227-0226","authenticated-orcid":false,"given":"Amit","family":"Kessel","sequence":"additional","affiliation":[{"name":"School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences Tel\u2010Aviv University  Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nir","family":"Ben\u2010Tal","sequence":"additional","affiliation":[{"name":"School of Neurobiology, Biochemistry and Biophysics, George S. 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