The dual enzyme LRRK2 hydrolyzes GTP in both its GTPase and kinase domains in vitro.

ABSTRACT: The evolutionarily conserved enzyme encoded by the leucine-rich repeat kinase 2 gene, LRRK2, harbors both a Rab-like GTPase domain and a serine/threonine protein kinase domain. Pathogenic mutations in either the GTPase or kinase domain can cause neurodegeneration and Parkinson disease. No high-resolution structure of the human LRRK2 kinase domain is available but the most common mutation, G2019S in the kinase domain, is predicted to alter the ATP-binding pocket structure and interaction with divalent cations. Here we find that the manganese-bound kinase domain acquires a robust ability to utilize both GTP as well as ATP in autophosphorylation of the GTPase domain and phosphorylation of peptide substrates in vitro. The G2019S LRRK2 mutation increases the efficiency of GTP-mediated kinase ac

SUBMITTER: Liu Z 

PROVIDER: S-EPMC5278637 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature