catalytic domain repeat 2 of bacterial cardiolipin synthase and similar proteins
This CD corresponds to the catalytic domain repeat 2 of bacterial cardiolipin synthase (CL synthase, EC 2.7.8.-) and a few homologs found in eukaryotes and archea. Bacterial CL synthases catalyze reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form cardiolipin (CL) and glycerol. The monomer of bacterial CL synthase consists of two catalytic domains. Each catalytic domain contains one copy of conserved HKD motifs (H-X-K-X(4)-D, X represents any amino acid residue) that are the characteristic of the phospholipase D (PLD) superfamily. Two HKD motifs from two domains together form a single active site involving in phosphatidyl group transfer. Bacterial CL synthases can be stimulated by phosphate and inhibited by CL, the product of the reaction, and by phosphatidate. Phosphate stimulation may be unique to enzymes with CL synthase activity in PLD superfamily. Like other PLD enzymes, bacterial CL synthase utilize a common two-step ping-pong catalytic mechanism involving an enzyme-substrate intermediate to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine residue from one HKD motif could function as the nucleophile attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid stabilizing the leaving group.
Comment:Based on similarity with phospholipase D, which functions as a bi-lobed monomer with two catalytic domains. Each domain carries one copy of the conserved HKD motif and two domains form a single active site.
Comment:The HKD signature motif (expanded to H-x-K-x(4)-D-x(6)-G-S/T-x-N in this subfamily, where x represents any amino acid residue) characterizes the PLD superfamily.
Comment:Most residues in the HKD motif are part of the active site.
Jiyao W et al.(2023). "The conserved domain database in 2023.",