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dc.contributor.authorŞensoy, Özge
dc.contributor.authorAtılgan, Ali Rana
dc.contributor.authorAtılgan, Canan
dc.identifier.citationŞensoy, Ö., Atılgan, A. ve Atılgan, C. (2017). FbpA iron storage and release are governed by periplasmic microenvironments. Physical Chmistry Chemical Physics, 19(8), 6064-6075.
dc.descriptionWOS: 000395869500041en_US
dc.descriptionPubMed ID: 28191562en_US
dc.description.abstractFerric binding protein (FbpA) is part of an elaborate iron piracy mechanism evolved in Gram-negative bacteria, shuttling iron in the periplasmic space, from the outer to the cytoplasmic membrane side. We address how the dissociation process of iron is facilitated, since the binding constant of iron is on the order of 10(18) M-1 at 6.5 pH and 200 mM ionic strength (IS). We monitor the conformational preferences of FbpA by extensive molecular dynamics (MD) simulations under conditions where IS, charge states of iron coordinating tyrosines and pH are varied, as well as when a mutation is introduced at an allosteric site. Steered MD is utilized to predict the binding affinity of iron. After triggering lobe opening by changing the charge states of tyrosines, the conformations adopted and the iron binding affinity still depend on pH, IS and allosteric interactions. To relate the observed conformational changes to the environmental conditions that might be encountered in the periplasmic space, we offer a plausible model that couples electrostatic potential distribution to the mechanical motions invoked. Although low pH/IS and allosteric perturbations decrease the affinity of iron, it remains high for spontaneous dissociation. However, the conformational changes modulated by the environmental conditions expose iron for chelation. Our study provides a quantitative dimension and molecular details to interpret the contribution of possible environmental conditions present in the periplasmic space to iron dissociation from FbpA, opening up the opportunity of modulating function via allosteric mutations or altering environmental conditions, thus offering a new route to developing strategies towards antibiotic resistance by targeting nutritional requirements.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey Projects [113Z408]en_US
dc.description.sponsorshipThis work was supported by the Scientific and Technological Research Council of Turkey Projects, grant no. 113Z408. We thank Gokce Guven for doing the initial MD calculations.en_US
dc.publisherRoyal Society of Chemistryen_US
dc.subjectFbpA Iron Storageen_US
dc.subjectPeriplasmic Microenvironmentsen_US
dc.titleFbpA iron storage and release are governed by periplasmic microenvironmentsen_US
dc.relation.journalPhysical Chmistry Chemical Physicsen_US
dc.departmentİstanbul Medipol Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Bilgisayar Mühendisliği Bölümüen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US

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