4q95 | pdb_00004q95

Crystal structure of HRASLS3/LRAT chimeric protein

spinqualitylabelsall models 4q95, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4q95 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SHV Related: 4dot Gene: HRASLS3, HREV107, human PLA2G16 and mouse Lrat, Lrat, PLA2G16 (HUMAN) Activity: Phosphatidylcholine--retinol O-acyltransferase, with EC number 2.3.1.135 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [HRSL3_HUMAN] Exhibits PLA1/2 activity, catalyzing the calcium-independent hydrolysis of acyl groups in various phosphatidylcholines (PC) and phosphatidylethanolamine (PE). For most substrates, PLA1 activity is much higher than PLA2 activity. Specifically catalyzes the release of fatty acids from phospholipids in adipose tissue (By similarity). N- and O-acylation activity is hardly detectable. Might decrease protein phosphatase 2A (PP2A) activity. Publication Abstract from PubMed Cellular uptake of vitamin A, production of visual chromophore and triglyceride homeostasis in adipocytes depend on two representatives of the vertebrate N1pC/P60 protein family, lecithin:retinol acyltransferase (LRAT) and HRAS-like tumor suppressor 3 (HRASLS3). Both proteins function as lipid-metabolizing enzymes but differ in their substrate preferences and dominant catalytic activity. The mechanism of this catalytic diversity is not understood. Here, by using a gain-of-function approach, we identified a specific sequence responsible for the substrate specificity of N1pC/P60 proteins. A 2.2-A crystal structure of the HRASLS3-LRAT chimeric enzyme in a thioester catalytic intermediate state revealed a major structural rearrangement accompanied by three-dimensional domain swapping dimerization not observed in native HRASLS proteins. Structural changes affecting the active site environment contributed to slower hydrolysis of the catalytic intermediate, supporting efficient acyl transfer. These findings reveal structural adaptation that facilitates selective catalysis and mechanism responsible for diverse substrate specificity within the LRAT-like enzyme family. LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3.,Golczak M, Sears AE, Kiser PD, Palczewski K Nat Chem Biol. 2015 Jan;11(1):26-32. doi: 10.1038/nchembio.1687. Epub 2014 Nov, 10. PMID:25383759 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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