6kz8 | pdb_00006kz8

Crystal structure of plant Phospholipase D alpha complex with phosphatidic acid

spinqualitylabelsall models 6kz8, resolution 2.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6kz8 is a 2 chain structure with sequence from Arath. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, PA8 Gene: PLDALPHA1, PLD1, At3g15730, MSJ11.13 (ARATH) Activity: Phospholipase D, with EC number 3.1.4.4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PLDA1_ARATH] Hydrolyzes glycerol-phospholipids at the terminal phosphodiesteric bond to generate phosphatidic acids (PA). Plays an important role in various cellular processes, including phytohormone action and response to stress, characterized by acidification of the cell (PubMed:9437863). Involved in wound induction of jasmonic acid (PubMed:11090221). May be involved in membrane lipid remodeling (PubMed:11239826). Probably involved in freezing tolerance by modulating the cold-responsive genes and accumulation of osmolytes (PubMed:16949955). Can use phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) as substrates, both in presence or in absence of PIP2 (PubMed:9578608). Its main substrate is phosphatidylcholine (PubMed:11239826). Stimulates the intrinsic GTPase activity of GPA1 upon binding (PubMed:14594812). Mediates the abscisic acid effects on stomata through interaction with GPA1 and the production of phosphatidic acid that bind to ABI1 (PubMed:17261695, PubMed:17565616). Involved in seed aging and deterioration (PubMed:17565616). Involved in microtubule stabilization and salt tolerance (PubMed:23150630). Involved in abscisic acid-induced stomatal closure (PubMed:22392280). Publication Abstract from PubMed Phospholipase D (PLD) hydrolyzes the phosphodiester bond of glycerophospholipids and produces phosphatidic acid (PA), which acts as a second messenger in many living organisms. A large number of PLDs have been identified in eukaryotes, and are viewed as promising targets for drug design because these enzymes are known to be tightly regulated and to function in the pathophysiology of many human diseases. However, the underlying molecular mechanisms of catalysis and regulation of eukaryotic PLD remain elusive. Here, we determined the crystal structure of full-length plant PLDalpha1 in the apo state and in complex with PA. The structure shows that the N-terminal C2 domain hydrophobically interacts with the C-terminal catalytic domain that features two HKD motifs. Our analysis reveals the catalytic site, substrate-binding mechanism, and a new Ca(2+)-binding site that is required for the activation of PLD. In addition, we tested several efficient small-molecule inhibitors against PLDalpha1, and suggested a possible competitive inhibition mechanism according to structure-based docking analysis. This study explains many long-standing questions about PLDs and provides structural insights into PLD-targeted inhibitor/drug design. Crystal structure of plant PLDalpha1 reveals catalytic and regulatory mechanisms of eukaryotic phospholipase D.,Li J, Yu F, Guo H, Xiong R, Zhang W, He F, Zhang M, Zhang P Cell Res. 2019 Oct 16. pii: 10.1038/s41422-019-0244-6. doi:, 10.1038/s41422-019-0244-6. PMID:31619765 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phospholipase D

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