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dc.contributor.authorAyyıldız, Merve
dc.contributor.authorÇeliker, Serkan
dc.contributor.authorÖzhelvacı, Fatih
dc.contributor.authorAkten, Ebru Demet
dc.date.accessioned2020-06-18T08:29:58Z
dc.date.available2020-06-18T08:29:58Z
dc.date.issued2020
dc.identifier.issn3247-8093
dc.identifier.issn2296-889X
dc.identifier.urihttps://doi.org/10.3389/fmolb.2020.00088en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12469/2924
dc.description.abstractThree allosteric glycolytic enzymes, phosphofructokinase, glyceraldehyde-3 phosphate dehydrogenase and pyruvate kinase, associated with bacterial, parasitic and human species, were explored to identify potential allosteric sites that would be used as prime targets for species-specific drug design purposes using a newly developed approach which incorporates solvent mapping, elastic network modeling, sequence and structural alignments. The majority of binding sites detected by solvent mapping overlapped with the interface regions connecting the subunits, thus appeared as promising target sites for allosteric regulation. Each binding site was then evaluated by its ability to alter the global dynamics of the receptor defined by the percentage change in the frequencies of the lowest-frequency modes most significantly and as anticipated, the most effective ones were detected in the vicinity of the well-reported catalytic and allosteric sites. Furthermore, some of our proposed regions intersected with experimentally resolved sites which are known to be critical for activity regulation, which further validated our approach. Despite the high degree of structural conservation encountered between bacterial/parasitic and human glycolytic enzymes, the majority of the newly presented allosteric sites exhibited a low degree of sequence conservation which further increased their likelihood to be used as species-specific target regions for drug design studies.en_US
dc.description.sponsorshipTubitaken_US
dc.language.isoEnglishen_US
dc.publisherFrontiers Mediaen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAllosteric regulationen_US
dc.subjectGlycolytic enzymeen_US
dc.subjectElastic network modelingen_US
dc.subjectSpecies-specificen_US
dc.subjectDrug discoveryen_US
dc.titleIdentification of Alternative Allosteric Sites in Glycolytic Enzymes for Potential Use as Species-Specific Drug Targetsen_US
dc.typeArticleen_US
dc.relation.journalFrontiers in Molecular Biosciencesen_US
dc.identifier.volume7en_US
dc.identifier.wosWOS:000537850000001en_US
dc.identifier.doi10.3389/fmolb.2020.00088en_US
dc.contributor.khasauthorAkten, Ebru Demeten_US
dc.contributor.khasauthorAyyıldız, Merve


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