Tunnel-like region observed as a potential allosteric site in<i> Staphylococcus</i><i> aureus</i> Glyceraldehyde-3-phosphate dehydrogenase
dc.authorid | Akten, Ebru Demet/0000-0002-0358-3171 | |
dc.authorscopusid | 58616916300 | |
dc.authorscopusid | 6504233664 | |
dc.authorscopusid | 6507297154 | |
dc.contributor.author | Akdoğan, Ebru Demet | |
dc.contributor.author | Kurkcuoglu, Ozge | |
dc.contributor.author | Akten, Ebru Demet | |
dc.date.accessioned | 2024-06-23T21:36:53Z | |
dc.date.available | 2024-06-23T21:36:53Z | |
dc.date.issued | 2024 | |
dc.department | Kadir Has University | en_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, Turkiye | en_US |
dc.description | Akten, Ebru Demet/0000-0002-0358-3171 | en_US |
dc.description.abstract | Glyceraldehyde 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.sponsorship | Scientific and Technological Research Council of Turkey [218M320] | en_US |
dc.description.sponsorship | This work has been partially supported by The Scientific and Technological Research Council of Turkey (TUBITAK Project #218M320) . | en_US |
dc.identifier.citation | 0 | |
dc.identifier.doi | 10.1016/j.abb.2023.109875 | |
dc.identifier.issn | 0003-9861 | |
dc.identifier.issn | 1096-0384 | |
dc.identifier.pmid | 38158117 | |
dc.identifier.scopus | 2-s2.0-85181095171 | |
dc.identifier.scopusquality | Q1 | |
dc.identifier.uri | https://doi.org/10.1016/j.abb.2023.109875 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12469/5663 | |
dc.identifier.volume | 752 | en_US |
dc.identifier.wos | WOS:001165630100001 | |
dc.identifier.wosquality | Q2 | |
dc.language.iso | en | en_US |
dc.publisher | Elsevier Science inc | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.rights | info:eu-repo/semantics/closedAccess | en_US |
dc.subject | Allostery | en_US |
dc.subject | Glycolytic enzyme | en_US |
dc.subject | Residue network model | en_US |
dc.subject | Low-frequency normal mode | en_US |
dc.subject | Communication pathway | en_US |
dc.title | Tunnel-like region observed as a potential allosteric site in<i> Staphylococcus</i><i> aureus</i> Glyceraldehyde-3-phosphate dehydrogenase | en_US |
dc.type | Article | en_US |
dspace.entity.type | Publication | |
relation.isAuthorOfPublication | 558d2b8e-c713-49e0-9350-d354abb5cd69 | |
relation.isAuthorOfPublication.latestForDiscovery | 558d2b8e-c713-49e0-9350-d354abb5cd69 |