4fa0
Crystal structure of human AdPLA to 2.65 A resolutionCrystal structure of human AdPLA to 2.65 A resolution
Structural highlights
FunctionPLAT3_HUMAN Exhibits both phospholipase A1/2 and acyltransferase activities (PubMed:19615464, PubMed:19047760, PubMed:22825852, PubMed:22605381, PubMed:26503625). Shows phospholipase A1 (PLA1) and A2 (PLA2) activity, catalyzing the calcium-independent release of fatty acids from the sn-1 or sn-2 position of glycerophospholipids (PubMed:19615464, PubMed:19047760, PubMed:22825852, PubMed:22605381, PubMed:22923616). For most substrates, PLA1 activity is much higher than PLA2 activity (PubMed:19615464). Shows O-acyltransferase activity,catalyzing the transfer of a fatty acyl group from glycerophospholipid to the hydroxyl group of lysophospholipid (PubMed:19615464). Shows N-acyltransferase activity, catalyzing the calcium-independent transfer of a fatty acyl group at the sn-1 position of phosphatidylcholine (PC) and other glycerophospholipids to the primary amine of phosphatidylethanolamine (PE), forming N-acylphosphatidylethanolamine (NAPE), which serves as precursor for N-acylethanolamines (NAEs) (PubMed:19615464, PubMed:19047760, PubMed:22825852, PubMed:22605381). Exhibits high N-acyltransferase activity and low phospholipase A1/2 activity (PubMed:22825852). Required for complete organelle rupture and degradation that occur during eye lens terminal differentiation, when fiber cells that compose the lens degrade all membrane-bound organelles in order to provide lens with transparency to allow the passage of light. Organelle membrane degradation is probably catalyzed by the phospholipase activity (By similarity).[UniProtKB:Q8R3U1][1] [2] [3] [4] [5] [6] (Microbial infection) Acts as a host factor for picornaviruses: required during early infection to promote viral genome release into the cytoplasm (PubMed:28077878). May act as a cellular sensor of membrane damage at sites of virus entry, which relocalizes to sites of membrane rupture upon virus unfection (PubMed:28077878). Facilitates safe passage of the RNA away from LGALS8, enabling viral genome translation by host ribosome (PubMed:28077878). May also be involved in initiating pore formation, increasing pore size or in maintaining pores for genome delivery (PubMed:28077878). The lipid-modifying enzyme activity is required for this process (PubMed:28077878).[7] Publication Abstract from PubMedAdipose phospholipase A(2) (AdPLA or Group XVI PLA(2)) plays an important role in the onset of obesity by suppressing adipose tissue lipolysis. As a consequence, AdPLA-deficient mice are resistant to obesity induced by high-fat diet or by leptin deficiency. It has been proposed that AdPLA mediates its anti-lipolytic effects by catalyzing the release of arachidonic acid. Based on sequence homology, AdPLA is part of a small family of acyltransferases and phospholipases related to lecithin:retinol acyltransferases (LRAT). To better understand the enzymatic mechanism of AdPLA and related LRAT proteins, we solved the crystal structure of AdPLA. Our model indicates that AdPLA is structurally related to the NlpC/P60 family of cysteine proteases, having its secondary structure elements configured in a circular permutation of the classic papain fold. Using both structural and biochemical evidence we demonstrate that the enzymatic activity of AdPLA is mediated by a distinctive Cys-His-His catalytic triad and that the C-terminal transmembrane domain of AdPLA is required for the interfacial catalysis. Analysis of the enzymatic activity of AdPLA toward synthetic and natural substrates indicates that AdPLA displays PLA(1) in addition to PLA(2) activity. Thus our results provide insight into the enzymatic mechanism and biochemical properties of AdPLA and LRAT-related proteins, and lead us to propose an alternate mechanism for AdPLA in promoting adipose tissue lipolysis that is not contingent on the release of arachidonic acid and which is compatible with its combined PLA(1)/A(2) activity. Structure/Function Relationships of Adipose Phospholipase A2 Containing a Cys-His-His Catalytic Triad.,Pang XY, Cao J, Addington L, Lovell S, Battaile KP, Zhang N, Rao JL, Dennis EA, Moise AR J Biol Chem. 2012 Aug 25. PMID:22923616[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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