Computational insights into iron coordination disruption in the human transferrin–neisseria meningitidis bacterial protein complex

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dc.authorid0000-0001-8603-3820
dc.authorid0000-0002-2037-3440
dc.authorid0000-0003-1345-0943
dc.authorid0000-0002-1465-7674
dc.authorid0000-0001-6043-4765
dc.contributor.authorDervişoğlu Özdemir, Celile
dc.contributor.authorDuran, Gizem Nur
dc.contributor.authorFındık, Volkan
dc.contributor.authorÖzbil, Mehmet
dc.contributor.authorSağ Erdem, Safiye
dc.date.accessioned2026-01-16T11:07:23Z
dc.date.available2026-01-16T11:07:23Z
dc.date.issued2025
dc.departmentFakülteler, Eczacılık Fakültesi, Eczacılık Meslek Bilimleri Bölümü, Analitik Kimya Ana Bilim Dalı
dc.description.abstractAmong many metal ions in biological systems, iron plays a fundamental role. Transferrins are iron-binding glycoproteins responsible for transporting Fe3+ in vertebrate blood. Neisse ria meningitidis, a Gram-negative pathogen causing meningitis, relies on iron for survival and acquires it from human transferrin (hTf) using two surface proteins, TbpA and TbpB. These proteins interact with hTf to form a ternary TbpA–TbpB–hTf complex, enabling iron capture from the host. The absence of an experimental crystal structure for this complex has hindered computational studies, a detailed understanding of Fe3+ dissociation, and designing efficient therapeutics. This study presents the first computational model of the ternary complex, its validation, and molecular dynamics simulations. Structural analyses revealed key electrostatic interactions regulating Fe3+ coordination and essential contact regions between proteins. The role of Lys359 from TbpA was investigated via QM/MM calculations by evaluating Fe3+ binding energies of isolated hTf, the ternary complex, and Lys359Ala, Lys359Arg, Lys359Asp mutant models. Results revealed that the proton trans fer from Lys359 leads to disruption of Tyr517–Fe3+ coordination, facilitating iron transfer to the bacterial system. Natural bond orbital analysis confirmed this mechanism. The findings provide new molecular insight into N. meningitidis iron acquisition and identify Lys359 as a potential target for covalent inhibitor design, guiding the development of novel therapeutics against meningococcal infection.
dc.description.sponsorshipThis work was supported by the Scientific and Technological Research Council of Türkiye (TÜB˙ITAK), Project no: 118Z353 and Project no: 223Z201. Bu çalışma, Türkiye Bilim ve Teknolojik Araştırma Konseyi (TÜBİTAK) tarafından 118Z353 ve 223Z201 numaralı projelerle desteklenmiştir.
dc.identifier.citationDervişoğlu Özdemir, C., Duran, G. N., Fındık, V., Özbil, M., & Sağ Erdem, S. (2025). Computational insights into iron coordination disruption in the human transferrin–neisseria meningitidis bacterial protein complex. Inorganics, 13(12), pp. 1-27. https://doi.org/10.3390/inorganics13120384
dc.identifier.doi10.3390/inorganics13120384
dc.identifier.endpage27
dc.identifier.issn2304-6740
dc.identifier.issue12
dc.identifier.scopusqualityQ2
dc.identifier.startpage1
dc.identifier.urihttps://doi.org/10.3390/inorganics13120384
dc.identifier.urihttps://hdl.handle.net/20.500.13055/1250
dc.identifier.volume13
dc.identifier.wosWOS:001646716800001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.indekslendigikaynak.otherSCI-E - Science Citation Index Expanded
dc.institutionauthorDervişoğlu Özdemir, Celile
dc.institutionauthorid0000-0001-8603-3820
dc.language.isoen
dc.publisherMDPI Publishing
dc.relation.ispartofInorganics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectNeisseria Meningitidis
dc.subjectTransferrin
dc.subjectTransferrin Binding Proteins
dc.subjectMolecular Dynamics Simulations
dc.subjectM06 Functional
dc.subjectDensity Functional Theory
dc.subjectONIOM
dc.titleComputational insights into iron coordination disruption in the human transferrin–neisseria meningitidis bacterial protein complex
dc.typeArticle
dspace.entity.typePublication

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