| http://purl.uniprot.org/citations/24591621 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24591621 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutation in leucine-rich-repeat kinase 2 (LRRK2) is a common cause of Parkinson disease (PD). A disease-causing point mutation R1441H/G/C in the GTPase domain of LRRK2 leads to overactivation of its kinase domain. However, the mechanism by which this mutation alters the normal function of its GTPase domain [Ras of complex proteins (Roc)] remains unclear. Here, we report the effects of R1441H mutation (RocR1441H) on the structure and activity of Roc. We show that Roc forms a stable monomeric conformation in solution that is catalytically active, thus demonstrating that LRRK2 is a bona fide self-contained GTPase. We further show that the R1441H mutation causes a twofold reduction in GTPase activity without affecting the structure, thermal stability, and GDP-binding affinity of Roc. However, the mutation causes a twofold increase in GTP-binding affinity of Roc, thus suggesting that the PD-causing mutation R1441H traps Roc in a more persistently activated state by increasing its affinity for GTP and, at the same time, compromising its GTP hydrolysis."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1323285111"xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Liu D."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Nichols R.J."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Wang M."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Zhang S."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Sahm H."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Liao J."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Vogel K.W."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Hoang Q.Q."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Zhang Z.Y."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Wu C.X."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Riddle S.M."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Federici M."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Cookson M.R."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Burlak C."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/author | "Stone T.A."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/pages | "4055-4060"xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/title | "Parkinson disease-associated mutation R1441H in LRRK2 prolongs the "active state" of its GTPase domain."xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://purl.uniprot.org/core/volume | "111"xsd:string |
| http://purl.uniprot.org/citations/24591621 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24591621 |
| http://purl.uniprot.org/citations/24591621 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24591621 |