4F0G

Crystal Structure of the Roco4 Kinase Domain from D. discoideum

Summary for 4F0G

• Entry DOI: 10.2210/pdb4f0g/pdb
• Related: 4F0F 4F1M 4F1O 4F1T
• Descriptor: Serine/threonine-protein kinase roco4 (2 entities in total)
• Functional Keywords: protein kinase, lrrk2, roco, atp-binding, nucleotide-binding, parkinson disease, serine/threonine-protein kinase, transferase, signaling protein
• Biological source: Dictyostelium discoideum (Slime mold)
• Total number of polymer chains: 1
• Total formula weight: 32616.54

Authors

Gilsbach, B.K.,Vetter, I.R.,Wittinghofer, A.,Kortholt, A. (deposition date: 2012-05-04, release date: 2012-06-27, Last modification date: 2023-09-13)

Primary citation

Gilsbach, B.K.,Ho, F.Y.,Vetter, I.R.,van Haastert, P.J.,Wittinghofer, A.,Kortholt, A.
Roco kinase structures give insights into the mechanism of Parkinson disease-related leucine-rich-repeat kinase 2 mutations.
Proc.Natl.Acad.Sci.USA, 109:10322-10327, 2012

PubMed Abstract: Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson disease. Here we show that Dictyostelium discoideum Roco4 is a suitable model to study the structural and biochemical characteristics of the LRRK2 kinase and can be used for optimization of current and identification of new LRRK2 inhibitors. We have solved the structure of Roco4 kinase wild-type, Parkinson disease-related mutants G1179S and L1180T (G2019S and I2020T in LRRK2) and the structure of Roco4 kinase in complex with the LRRK2 inhibitor H1152. Taken together, our data give important insight in the LRRK2 activation mechanism and, most importantly, explain the G2019S-related increase in LRRK2 kinase activity.

PubMed: 22689969
DOI: 10.1073/pnas.1203223109

Experimental method

X-RAY DIFFRACTION (2 Å)