The pyridoxal 5' | 合法醫療器材資訊網
由AEBeattie著作·2013·被引用12次—1EastChemSchoolofChemistry,TheUniversityofEdinburgh,WestMainsRoad,...Thepyridoxal5'-phosphate(PLP)-dependentenzymeserinepalmitoyltransferase...ResearchSupport,N.I.H.,Extramural;ResearchSupp
The pyridoxal 5-phosphate (PLP)-dependent enzyme serine palmitoyltransferase (SPT) catalyses the first step of de novo sphingolipid biosynthesis. The core human enzyme is a membrane-bound heterodimer composed of two subunits (hLCB1 and hLCB2a/b), and mutations in both hLCB1 (e.g., C133W and C133Y) and hLCB2a (e.g., V359M, G382V, and I504F) have been identified in patients with hereditary sensory and autonomic neuropathy type I (HSAN1), an inherited disorder that affects sensory and autonomic neurons. These mutations result in substrate promiscuity, leading to formation of neurotoxic deoxysphingolipids found in affected individuals. Here we measure the activities of the hLCB2a mutants in the presence of ssSPTa and ssSPTb and find that all decrease enzyme activity. High resolution structural data of the homodimeric SPT enzyme from the bacterium Sphingomonas paucimobilis (Sp SPT) provides a model to understand the impa...
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