6KZ9

Crystal structure of plant Phospholipase D alpha

Summary for 6KZ9

• Entry DOI: 10.2210/pdb6kz9/pdb
• Descriptor: Phospholipase D alpha 1, CALCIUM ION (3 entities in total)
• Functional Keywords: phospholipase d, calcium activation, c2 domain, phosphatidic acid, inhibitor, hydrolase
• Biological source: Arabidopsis thaliana (Mouse-ear cress)
• Total number of polymer chains: 1
• Total formula weight: 92008.06

Authors

Li, J.X.,Yu, F.,Zhang, P. (deposition date: 2019-09-23, release date: 2019-10-30, Last modification date: 2024-03-27)

Primary citation

Li, J.,Yu, F.,Guo, H.,Xiong, R.,Zhang, W.,He, F.,Zhang, M.,Zhang, P.
Crystal structure of plant PLD alpha 1 reveals catalytic and regulatory mechanisms of eukaryotic phospholipase D.
Cell Res., 30:61-69, 2020

PubMed Abstract: 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 PLDα1 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-binding site that is required for the activation of PLD. In addition, we tested several efficient small-molecule inhibitors against PLDα1, 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.

PubMed: 31619765
DOI: 10.1038/s41422-019-0244-6

Experimental method

X-RAY DIFFRACTION (1.801 Å)