title: Conserved sequence motifs and the structure of the mTOR kinase domain.
abstract: The atypical serine/threonine kinase mTOR (mammalian target of rapamycin) is a central regulator of cell growth and metabolism. mTOR is part of two multisubunit signalling complexes, mTORC1 and mTORC2. Although many aspects of mTOR signalling are understood, the lack of high-resolution structures impairs a detailed understanding of complex assembly, function and regulation. The structure of the kinase domain is of special interest for the development of mTOR inhibitors as anti-cancer agents. A homology model of the mTOR kinase domain was derived from the structure of PI3Ks (phosphoinositide 3-kinases). More recently, the crystal structure of the catalytic domain of human mTOR was determined, providing long-awaited structural insight into the architecture of mTOR. Interestingly, the homology model predicted several aspects of the crystal structure. In the present paper, we revisit the homology model in the context of the now available crystal structure of the mTOR kinase domain.
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Sauer
authors.forename: Stefan
authors.initials: S
authors.lastname: Imseng
authors.forename: Timm
authors.initials: T
authors.lastname: Maier
authors.forename: Michael N
authors.initials: MN
authors.lastname: Hall
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D017124:Conserved Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000255:Adenosine Triphosphate; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases