Phosphoryl transfer reaction catalyzed by membrane diacylglycerol kinase: a theoretical mechanism study

摘要: Diacylglycerol kinase is an integral membrane protein which catalyzes phosphoryl transfer from ATP to diacylglycerol. As the smallest known, it shares no sequence homology with conventional kinases and possesses a distinct trimer structure. Thus far, its catalytic mechanism remains elusive. Using molecular dynamics quantum mechanics calculations, we investigated co-factor substrate binding mechanism. Based on analysis of density functional theory reveal that phosphorylation reaction diacylglycerol features same as other kinases, despite unique structural properties. Our results further show active site relatively open able accommodate ligands in multiple orientations, suggesting optimization orientations conformational changes would occur prior actual transfer.