{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gilsbach BK"],"funding":["Michael J. Fox Foundation for Parkinson's Research"],"pagination":["RP91083"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11658767"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12"],"pubmed_abstract":["The Parkinson's disease (PD)-linked protein Leucine-Rich Repeat Kinase 2 (LRRK2) consists of seven domains, including a kinase and a Roc G domain. Despite the availability of several high-resolution structures, the dynamic regulation of its unique intramolecular domain stack is nevertheless still not well understood. By in-depth biochemical analysis, assessing the Michaelis-Menten kinetics of the Roc G domain, we have confirmed that LRRK2 has, similar to other Roco protein family members, a K<sub>M</sub> value of LRRK2 that lies within the range of the physiological GTP concentrations within the cell. Furthermore, the R1441G PD variant located within a mutational hotspot in the Roc domain showed an increased catalytic efficiency. In contrast, the most common PD variant G2019S, located in t"],"journal":["eLife"],"pubmed_title":["Intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase-dependent mechanism."],"pmcid":["PMC11658767"],"funding_grant_id":["8068.04"],"pubmed_authors":["Gloeckner CJ","Gilsbach BK","Guaitoli G","Ho FY","Kortholt A","Zhang X","Riebenbauer B"],"additional_accession":[]},"is_claimable":false,"name":"Intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase-dependent mechanism.","description":"The Parkinson's disease (PD)-linked protein Leucine-Rich Repeat Kinase 2 (LRRK2) consists of seven domains, including a kinase and a Roc G domain. Despite the availability of several high-resolution structures, the dynamic regulation of its unique intramolecular domain stack is nevertheless still not well understood. By in-depth biochemical analysis, assessing the Michaelis-Menten kinetics of the Roc G domain, we have confirmed that LRRK2 has, similar to other Roco protein family members, a K<sub>M</sub> value of LRRK2 that lies within the range of the physiological GTP concentrations within the cell. Furthermore, the R1441G PD variant located within a mutational hotspot in the Roc domain showed an increased catalytic efficiency. In contrast, the most common PD variant G2019S, located in t","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-06-01T19:41:11.721Z","creation":"2025-04-06T22:16:04.084Z"},"accession":"S-EPMC11658767","cross_references":{"pubmed":["39699947"],"doi":["10.7554/eLife.91083"]}}