5l2q
Serine/threonine-protein kinase 40 (STK40) kinase homology domain
Structural highlights
FunctionSTK40_HUMAN May be a negative regulator of NF-kappa-B and p53-mediated gene transcription.[1] Publication Abstract from PubMedSerine/threonine kinase 40 (STK40) was originally identified as a distant homolog of Tribbles-family proteins. Despite accumulating data attesting to the importance of STK40 in a variety of different physiologic processes, little is known about its biological activity or mechanism of action. Here, we show that STK40 interacts with Constitutive Photomorphogenic Protein 1 (COP1), relying primarily on a C-terminal sequence analogous to the motif found in Tribbles proteins. In order to further elucidate structure-function relationships in STK40, we determined the crystal structure of the STK40 kinase homology domain at 2.5 A resolution. The structure, together with ATP-binding assay results, show that STK40 is a pseudokinase, in which substitutions of conserved residues within the kinase domain prevent ATP binding. Although the structure of the kinase homology domain diverges from the analogous region of Trib1, the results reported here suggest functional parallels between STK40 and Tribbles-family proteins as COP1 adaptors. STK40 Is a Pseudokinase that Binds the E3 Ubiquitin Ligase COP1.,Durzynska I, Xu X, Adelmant G, Ficarro SB, Marto JA, Sliz P, Uljon S, Blacklow SC Structure. 2016 Dec 24. pii: S0969-2126(16)30398-7. doi:, 10.1016/j.str.2016.12.008. PMID:28089446[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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