Computational Insights into Iron Coordination Disruption in the Human Transferrin–Neisseria meningitidis Bacterial Protein Complex
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| الحاوية / القاعدة: | Inorganics vol. 13, no. 12 (2025), p. 384-411 |
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| المؤلف الرئيسي: | |
| مؤلفون آخرون: | , , , |
| منشور في: |
MDPI AG
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| الموضوعات: | |
| الوصول للمادة أونلاين: | Citation/Abstract Full Text + Graphics Full Text - PDF |
| الوسوم: |
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| 022 | |a 2304-6740 | ||
| 024 | 7 | |a 10.3390/inorganics13120384 |2 doi | |
| 035 | |a 3286306635 | ||
| 045 | 2 | |b d20250101 |b d20251231 | |
| 084 | |a 231642 |2 nlm | ||
| 100 | 1 | |a Dervişoğlu Özdemir Celile |u Department of Analytical Chemistry, Faculty of Pharmacy, Istanbul Health and Technology University, Sütlüce Campus, Istanbul 34445, Türkiye; celile.dervisoglu@istun.edu.tr | |
| 245 | 1 | |a Computational Insights into Iron Coordination Disruption in the Human Transferrin–<i>Neisseria meningitidis</i> Bacterial Protein Complex | |
| 260 | |b MDPI AG |c 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Among many metal ions in biological systems, iron plays a fundamental role. Transferrins are iron-binding glycoproteins responsible for transporting Fe3+ in vertebrate blood. Neisseria 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 transfer 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. | |
| 653 | |a Physiology | ||
| 653 | |a Crystal structure | ||
| 653 | |a Iron | ||
| 653 | |a Glycoproteins | ||
| 653 | |a Protons | ||
| 653 | |a Ferric ions | ||
| 653 | |a Meningitis | ||
| 653 | |a Computer applications | ||
| 653 | |a Electrostatic properties | ||
| 653 | |a Transferrins | ||
| 653 | |a Coordination | ||
| 653 | |a Drug development | ||
| 653 | |a Transferrin | ||
| 653 | |a Drug resistance | ||
| 653 | |a Proteins | ||
| 653 | |a Simulation | ||
| 653 | |a Signal transduction | ||
| 653 | |a Quantum physics | ||
| 653 | |a Disruption | ||
| 653 | |a Ligands | ||
| 653 | |a Metal ions | ||
| 653 | |a Molecular dynamics | ||
| 653 | |a Enzymes | ||
| 653 | |a Vertebrates | ||
| 653 | |a Neisseria meningitidis | ||
| 700 | 1 | |a Duran, Gizem Nur |u Institute of Biotechnology, Gebze Technical University, Kocaeli 41400, Türkiye; g.duran2022@gtu.edu.tr | |
| 700 | 1 | |a Fındık Volkan |u Department of Chemistry, Faculty of Sciences, Marmara University, Göztepe Campus, Istanbul 34722, Türkiye; volkan.findik@marmara.edu.tr | |
| 700 | 1 | |a Özbil Mehmet |u Institute of Biotechnology, Gebze Technical University, Kocaeli 41400, Türkiye; g.duran2022@gtu.edu.tr | |
| 700 | 1 | |a Sağ Erdem Safiye |u Department of Chemistry, Faculty of Sciences, Marmara University, Göztepe Campus, Istanbul 34722, Türkiye; volkan.findik@marmara.edu.tr | |
| 773 | 0 | |t Inorganics |g vol. 13, no. 12 (2025), p. 384-411 | |
| 786 | 0 | |d ProQuest |t Materials Science Database | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3286306635/abstract/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text + Graphics |u https://www.proquest.com/docview/3286306635/fulltextwithgraphics/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3286306635/fulltextPDF/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |