Catalytic domain of EDTA-resistant nuclease Nuc, vertebrate phospholipase D6, and similar proteins
Catalytic domain of EDTA-resistant nuclease Nuc, vertebrate phospholipase D6 (PLD6, EC 3.1.4.4), and similar proteins. Nuc is an endonuclease from Salmonella typhimurium and the smallest known member of the PLD superfamily. It cleaves both single- and double-stranded DNA. PLD6 selectively hydrolyzes the terminal phosphodiester bond of phosphatidylcholine (PC), with the formation of phosphatidic acid and alcohols. Phosphatidic acid is an essential compound involved in signal transduction. PLD6 also catalyzes the transphosphatidylation of phospholipids to acceptor alcohols, by which various phospholipids can be synthesized. Both Nuc and PLD6 belong to the phospholipase D (PLD) superfamily. They contain a short conserved sequence motif, the HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which is essential for catalysis. PLDs utilize a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit. This subfamily also includes some uncharacterized hypothetical proteins, which have two HKD motifs in a single polypeptide chain.
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