Publication: Structural characterization of TRAF6 N-terminal for therapeutic uses and computational studies on new derivatives
dc.contributor.coauthor | Sever, Belgin | |
dc.contributor.coauthor | Basoglu-Unal, Faika | |
dc.contributor.coauthor | Ece, Abdulilah | |
dc.contributor.coauthor | Tateishi, Hiroshi | |
dc.contributor.coauthor | Koga, Ryoko | |
dc.contributor.coauthor | Radwan, Mohamed O. | |
dc.contributor.coauthor | Demir, Nefise | |
dc.contributor.coauthor | Can, Mustafa | |
dc.contributor.coauthor | Aytemir, Mutlu Dilsiz | |
dc.contributor.coauthor | Inoue, Jun-ichiro | |
dc.contributor.coauthor | Otsuka, Masami | |
dc.contributor.coauthor | Fujita, Mikako | |
dc.contributor.department | Department of Molecular Biology and Genetics | |
dc.contributor.department | KUISCID (Koç University İşbank Center for Infectious Diseases) | |
dc.contributor.department | Graduate School of Sciences and Engineering | |
dc.contributor.kuauthor | Demirci, Hasan | |
dc.contributor.kuauthor | Çiftçi, Halil İbrahim | |
dc.contributor.kuauthor | Güven, Ömür | |
dc.contributor.schoolcollegeinstitute | College of Sciences | |
dc.contributor.schoolcollegeinstitute | GRADUATE SCHOOL OF SCIENCES AND ENGINEERING | |
dc.contributor.schoolcollegeinstitute | Research Center | |
dc.date.accessioned | 2025-01-19T10:30:12Z | |
dc.date.issued | 2023 | |
dc.description.abstract | Tumor necrosis factor receptor-associated factors (TRAFs) are a protein family with a wide variety of roles and binding partners. Among them, TRAF6, a ubiquitin ligase, possesses unique receptor binding specificity and shows diverse functions in immune system regulation, cellular signaling, central nervous system, and tumor formation. TRAF6 consists of an N-terminal Really Interesting New Gene (RING) domain, multiple zinc fingers, and a C-terminal TRAF domain. TRAF6 is an important therapeutic target for various disorders and structural studies of this protein are crucial for the development of next-generation therapeutics. Here, we presented a TRAF6 N-terminal structure determined at the Turkish light source "Turkish DeLight" to be 3.2 angstrom resolution at cryogenic temperature (PDB ID: 8HZ2). This structure offers insight into the domain organization and zinc-binding, which are critical for protein function. Since the RING domain and the zinc fingers are key targets for TRAF6 therapeutics, structural insights are crucial for future research. Separately, we rationally designed numerous new compounds and performed molecular docking studies using this template (PDB ID:8HZ2). According to the results, 10 new compounds formed key interactions with essential residues and zinc ion in the N-terminal region of TRAF6. Molecular dynamic (MD) simulations were performed for 300 ns to evaluate the stability of three docked complexes (compounds 256, 322, and 489). Compounds 256 and 489 was found to possess favorable bindings with TRAF6. These new compounds also showed moderate to good pharmacokinetic profiles, making them potential future drug candidates as TRAF6 inhibitors. | |
dc.description.indexedby | WOS | |
dc.description.indexedby | Scopus | |
dc.description.indexedby | PubMed | |
dc.description.issue | 11 | |
dc.description.openaccess | Green Published, gold | |
dc.description.publisherscope | International | |
dc.description.sponsoredbyTubitakEu | N/A | |
dc.description.sponsorship | Authors would like to dedicate this manuscript to the memory of Albert E. Dahlberg and Nizar Turker. The authors gratefully acknowledge the use of the services and Turkish Light Source (Turkish DeLight) X-ray facility at the University of Health Sciences, Experimental Medicine Application & Research Center, Validebag Research Park. Coordinates of the TRAF6 N-terminal structure have been deposited in the Protein Data Bank under accession codes 8HZ2. | |
dc.description.volume | 16 | |
dc.identifier.doi | 10.3390/ph16111608 | |
dc.identifier.eissn | 1424-8247 | |
dc.identifier.quartile | Q1 | |
dc.identifier.scopus | 2-s2.0-85178372037 | |
dc.identifier.uri | https://doi.org/10.3390/ph16111608 | |
dc.identifier.uri | https://hdl.handle.net/20.500.14288/26008 | |
dc.identifier.wos | 1114535900001 | |
dc.keywords | TRAF6 | |
dc.keywords | Zinc finger | |
dc.keywords | RING domain | |
dc.keywords | Cancer | |
dc.keywords | X-ray crystallography | |
dc.keywords | Structural biology | |
dc.keywords | Turkish light source "Turkish DeLight" | |
dc.keywords | Molecular modelling | |
dc.keywords | Pharmacokinetic determinants | |
dc.language.iso | eng | |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | |
dc.relation.grantno | TBIdot;TAK 1001 program | |
dc.relation.ispartof | Pharmaceuticals | |
dc.subject | Chemistry, medicinal | |
dc.subject | Pharmacology and pharmacy | |
dc.title | Structural characterization of TRAF6 N-terminal for therapeutic uses and computational studies on new derivatives | |
dc.type | Journal Article | |
dspace.entity.type | Publication | |
local.contributor.kuauthor | Demirci, Hasan | |
local.contributor.kuauthor | Güven, Ömür | |
local.contributor.kuauthor | Çiftçi, Halil İbrahim | |
local.publication.orgunit1 | College of Sciences | |
local.publication.orgunit1 | GRADUATE SCHOOL OF SCIENCES AND ENGINEERING | |
local.publication.orgunit1 | Research Center | |
local.publication.orgunit2 | Department of Molecular Biology and Genetics | |
local.publication.orgunit2 | KUISCID (Koç University İşbank Center for Infectious Diseases) | |
local.publication.orgunit2 | Graduate School of Sciences and Engineering | |
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