title: In vitro and in silico studies on substrate recognition and acceptance of human PKMYT1, a Cdk1 inhibitory kinase.
abstract: The human Myt1 kinase (PKMYT1) is an important regulator of the G2/M transition in the cell cycle. Presently, limited knowledge about its substrate recognition is available. Here, various potential substrates were investigated by different antibody based techniques including fluorescence polarization immunoassays and immunoblotting. Regarding both Thr and Tyr kinase activity, only protein substrates were found to be phosphorylated by Myt1, whereas any tested peptide was not recognized. In silico molecular dynamics studies were used to compare the stability of the Myt1 peptide complex with Wee1 peptide complex and support the biochemical findings. Furthermore, a Myt1 kinase binding assay suggests Myt1 being insensitive to staurosporine.
authors.affiliation: Department of Medicinal Chemistry, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rohe
authors.forename: Frank
authors.initials: F
authors.lastname: Erdmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Bäßler
authors.forename: Kanin
authors.initials: K
authors.lastname: Wichapong
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sippl
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D016231:Fluorescence Polarization Immunoassay; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D011505:Protein-Tyrosine Kinases; C490679:PKMYT1 protein, human; D017346:Protein Serine-Threonine Kinases