Homology modeling and ligand docking of Mitogen-activated protein kinase-activated protein kinase 5 (MK5)
ForfatterLindin, Inger; Wuxiuer, Yimingjiang; Kufareva, Irina; Abagyan, Ruben; Moens, Ugo; Sylte, Ingebrigt; Ravna, Aina Westrheim
Background: Mitogen-activated protein kinase-activated protein kinase 5 (MK5) is involved in one of the major signaling pathways in cells, the mitogen-activated protein kinase pathway. MK5 was discovered in 1998 by the groups of Houng Ni and Ligou New, and was found to be highly conserved throughout the vertebrates. Studies, both in vivo and in vitro, have shown that it is implicated in tumor suppression as well as tumor promotion, embryogenesis, anxiety, locomotion, cell motility and cell cycle regulation. Methods: In order to obtain a molecular model of MK5 that can be used as a working tool for development of chemical probes, three MK5 models were constructed and refined based on three different known crystal structures of the closely related MKs; MK2 [PDB: 2OZA and PDB: 3M2W] and MK3 [PDB: 3FHR]. The main purpose of the present MK5 molecular modeling study was to identify the best suited template for making a MK5 model. The ability of the generated models to effectively discriminate between known inhibitors and decoys was analyzed using receiver operating characteristic (ROC) curves. Results: According to the ROC curve analyzes, the refined model based on 3FHR was most effective in discrimination between known inhibitors and decoys. Conclusions: The 3FHR-based MK5 model may serve as a working tool for development of chemical probes using computer aided drug design. The biological function of MK5 still remains elusive, but its role as a possible drug target may be elucidated in the near future.
SiteringTheoretical Biology and Medical Modelling (2013), vol. 10:56
Følgende lisensfil er knyttet til denne innførselen:
Viser innførsler relatert til tittel, forfatter og emneord.
Prognostic Impacts of Angiopoietins in NSCLC Tumor Cells and Stroma : VEGF-A Impact Is Strongly Associated with Ang-2 Andersen, Sigve; Dønnem, Tom; Al-Shibli, Khalid Ibrahim; Al-Saad, Samer; Stenvold, Helge; Busund, Lill-Tove; Bremnes, Roy M. (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)Angiopoietins and their receptor Tie-2 are, in concert with VEGF-A, key mediators in angiogenesis. This study evaluates the prognostic impact of all known human angiopoietins (Ang-1, Ang-2 and Ang-4) and their receptor ...
Humant papillomavirus : en litteraturstudie om HPV, dets relasjon til cancer og tiltak mot videre spredning av virus Gabrielsen, Endre (Master thesis; Mastergradsoppgave, 2012-06-01)I 1983 oppdaget zur Hausen sammenhengen mellom Humant Papillomavirus (HPV) og livmorhalskreft. På denne tiden visste man ikke at det var HPV som var årsaken til at Helaceller kunne leve in vitro. Ny forskning relaterer ...
Hoem, Gry (Master thesis; Mastergradsoppgave, 2012-06)Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5’ un-translated portion of the fragile mental retardation 1 gene (FMR1) leading to deficiency or absence of the FMR1 protein (FMRP). FMRP ...