3rlh
Crystal structure of a class II phospholipase D from Loxosceles intermedia venomCrystal structure of a class II phospholipase D from Loxosceles intermedia venom
Structural highlights
FunctionA1HA_LOXIN Catalyzes the hydrolysis of sphingomyelin, lysophosphatidylcholine, and lyso-platelet activating factor but not that of phosphatidylcholine. Shows a high enzymatic activity. Induces dermonecrosis, blood vessel permeability and platelet aggregation (PubMed:9790962). Is directly toxic to kidney (PubMed:16005484) and liver (PubMed:18765244). Also induces hemolysis in a complement-dependent manner (PubMed:9790962) as well as in a complement-independent manner. The hemolysis provoked in a complement-independent manner is composed of several steps. The toxin binds to erythrocyte membranes, hydrolyzes membrane phospholipids (sphingomyelin and lysophosphatidylcholine) thus generating metabolism products that cause hemolysis, probably by provoking an increase of calcium inside cells. The calcium influx is due to the opening of L-type calcium channels, since L-type calcium channel blockers inhibit calcium influx (PubMed:21590705).[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedPhospholipases D (PLDs) are principally responsible for the local and systemic effects of Loxosceles envenomation including dermonecrosis and hemolysis. Despite their clinical relevance in loxoscelism, to date, only the SMase I from Loxosceles laeta, a class I member, has been structurally characterized. The crystal structure of a class II member from Loxosceles intermedia venom has been determined at 1.7A resolution. Structural comparison to the class I member showed that the presence of an additional disulphide bridge which links the catalytic loop to the flexible loop significantly changes the volume and shape of the catalytic cleft. An examination of the crystal structures of PLD homologues in the presence of low molecular weight compounds at their active sites suggests the existence of a ligand-dependent rotamer conformation of the highly conserved residue Trp230 (equivalent to Trp192 in the glycerophosphodiester phosphodiesterase from Thermus thermophofilus, PDB code: 1VD6) indicating its role in substrate binding in both enzymes. Sequence and structural analyses suggest that the reduced sphingomyelinase activity observed in some class IIb PLDs is probably due to point mutations which lead to a different substrate preference. Structure of a novel class II phospholipase D: Catalytic cleft is modified by a disulphide bridge.,de Giuseppe PO, Ullah A, Silva DT, Gremski LH, Wille AC, Chaves Moreira D, Ribeiro AS, Chaim OM, Murakami MT, Veiga SS, Arni RK Biochem Biophys Res Commun. 2011 Jun 17;409(4):622-7. Epub 2011 May 17. PMID:21616057[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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