Tunnel-like region observed as a potential allosteric site in<i> Staphylococcus</i><i> aureus</i> Glyceraldehyde-3-phosphate dehydrogenase

dc.authoridAkten, Ebru Demet/0000-0002-0358-3171
dc.authorscopusid58616916300
dc.authorscopusid6504233664
dc.authorscopusid6507297154
dc.contributor.authorAkdoğan, Ebru Demet
dc.contributor.authorKurkcuoglu, Ozge
dc.contributor.authorAkten, Ebru Demet
dc.date.accessioned2024-06-23T21:36:53Z
dc.date.available2024-06-23T21:36:53Z
dc.date.issued2024
dc.departmentKadir Has Universityen_US
dc.department-temp[Guner-Yilmaz, Ozde Zeynep; Kurkcuoglu, Ozge] Istanbul Tech Univ, Dept Chem Engn, Istanbul, Turkiye; [Akten, Ebru Demet] Kadir Has Univ, Fac Engn & Nat Sci, Dept Mol Biol & Genet, Istanbul, Turkiyeen_US
dc.descriptionAkten, Ebru Demet/0000-0002-0358-3171en_US
dc.description.abstractGlyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzing the sixth step of glycolysis has been investigated for allosteric features that might be used as potential target for specific inhibition of Staphylococcus aureus (S.aureus). X-ray structure of bacterial enzyme for which a tunnel-like opening passing through the center previously proposed as an allosteric site has been subjected to six independent 500 ns long Molecular Dynamics simulations. Harmonic bond restraints were employed at key residues to underline the allosteric feature of this region. A noticeable reduction was observed in the mobility of NAD+ binding domains when restrictions were applied. Also, a substantial decrease in cross-correlations between distant C alpha fluctuations was detected throughout the structure. Mutual information (MI) analysis revealed a similar decrease in the degree of correspondence in positional fluctuations in all directions everywhere in the receptor. MI between backbone and sidechain torsional variations changed its distribution profile and decreased considerably around the catalytic sites when restraints were employed. Principal component analysis clearly showed that the restrained state sampled a narrower range of conformations than apo state, especially in the first principal mode due to restriction in the conformational flexibility of NAD+ binding domain. Clustering the trajectory based on catalytic site residues displayed a smaller repertoire of conformations for restrained state compared to apo. Representative snapshots subjected to k-shortest pathway analysis revealed the impact of bond restraints on the allosteric communication which displayed distinct optimal and suboptimal pathways for two states, where observed frequencies of critical residues Gln51 and Val283 at the proposed site changed considerably.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey [218M320]en_US
dc.description.sponsorshipThis work has been partially supported by The Scientific and Technological Research Council of Turkey (TUBITAK Project #218M320) .en_US
dc.identifier.citation0
dc.identifier.doi10.1016/j.abb.2023.109875
dc.identifier.issn0003-9861
dc.identifier.issn1096-0384
dc.identifier.pmid38158117
dc.identifier.scopus2-s2.0-85181095171
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.abb.2023.109875
dc.identifier.urihttps://hdl.handle.net/20.500.12469/5663
dc.identifier.volume752en_US
dc.identifier.wosWOS:001165630100001
dc.identifier.wosqualityQ2
dc.language.isoenen_US
dc.publisherElsevier Science incen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAllosteryen_US
dc.subjectGlycolytic enzymeen_US
dc.subjectResidue network modelen_US
dc.subjectLow-frequency normal modeen_US
dc.subjectCommunication pathwayen_US
dc.titleTunnel-like region observed as a potential allosteric site in<i> Staphylococcus</i><i> aureus</i> Glyceraldehyde-3-phosphate dehydrogenaseen_US
dc.typeArticleen_US
dspace.entity.typePublication
relation.isAuthorOfPublication558d2b8e-c713-49e0-9350-d354abb5cd69
relation.isAuthorOfPublication.latestForDiscovery558d2b8e-c713-49e0-9350-d354abb5cd69

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