4F1T

Crystal Structure of the Roco4 Kinase Domain from D. discoideum bound to the ROCK Inhibitor H1152

4F1T の概要

• エントリーDOI: 10.2210/pdb4f1t/pdb
• 関連するPDBエントリー: 4F0F 4F0G 4F1M 4F1O
• 分子名称: Serine/threonine-protein kinase roco4, (S)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLINE)SULFONYL]-HOMOPIPERAZINE (3 entities in total)
• 機能のキーワード: protein kinase, lrrk2, roco, kinase, atp-binding, nucleotide-binding, serine/threonine-protein kinase, transferase, signaling protein, signaling protein-inhibitor complex, signaling protein/inhibitor
• 由来する生物種: Dictyostelium discoideum (Slime mold)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33255.38

構造登録者

Gilsbach, B.K.,Vetter, I.R.,Wittinghofer, A.,Kortholt, A. (登録日: 2012-05-07, 公開日: 2012-06-27, 最終更新日: 2023-09-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.3 Å)