Zinc-dependent phospholipase C explained

In molecular biology, zinc-dependent phospholipases C is a family of bacterial phospholipases C enzymes, some of which are also known as alpha toxins.

Bacillus cereus contains a monomeric phospholipase C (PLC) of 245 amino-acid residues. Although PLC prefers to act on phosphatidylcholine, it also shows weak catalytic activity with sphingomyelin and phosphatidylinositol.^[1] Sequence studies have shown the protein to be similar both to alpha toxin from Clostridium perfringens and Clostridium bifermentans, a phospholipase C involved in haemolysis and cell rupture,^[2] and to lecithinase from Listeria monocytogenes, which aids cell-to-cell spread by breaking down the 2-membrane vacuoles that surround the bacterium during transfer.^[3]

Each of these proteins is a zinc-dependent enzyme, binding 3 zinc ions per molecule.^[4] The enzymes catalyse the conversion of phosphatidylcholine and water to 1,2-diacylglycerol and choline phosphate.

In Bacillus cereus, there are nine residues known to be involved in binding the zinc ions: 5 His, 2 Asp, 1 Glu and 1 Trp. These residues are all conserved in the Clostridium alpha-toxin.

Some examples of this enzyme contain a C-terminal sequence extension that contains a PLAT domain which is thought to be involved in membrane localisation.^{[5] [6]}

Notes and References

1. Nakamura S, Yamada A, Tsukagoshi N, Udaka S, Sasaki T, Makino S, Little C, Tomita M, Ikezawa H . Nucleotide sequence and expression in Escherichia coli of the gene coding for sphingomyelinase of Bacillus cereus . Eur. J. Biochem. . 175 . 2 . 213–220 . 1988 . 2841128 . 10.1111/j.1432-1033.1988.tb14186.x.
2. Titball RW, Rubidge T, Hunter SE, Martin KL, Morris BC, Shuttleworth AD, Anderson DW, Kelly DC . Molecular cloning and nucleotide sequence of the alpha-toxin (phospholipase C) of Clostridium perfringens . Infect. Immun. . 57 . 2 . 367–376 . 1989 . 10.1128/IAI.57.2.367-376.1989 . 2536355 . 313106.
3. Kocks C, Dramsi S, Ohayon H, Geoffroy C, Mengaud J, Cossart P, Vazquez-Boland JA . Nucleotide sequence of the lecithinase operon of Listeria monocytogenes and possible role of lecithinase in cell-to-cell spread . Infect. Immun. . 60 . 1 . 219–230 . 1992 . 10.1128/IAI.60.1.219-230.1992 . 1309513 . 257526.
4. Titball RW, Rubidge T . The role of histidine residues in the alpha toxin of Clostridium perfringens . FEMS Microbiol. Lett. . 56 . 3 . 261–265 . 1990 . 2111259 . 10.1111/j.1574-6968.1988.tb03188.x. free .
5. Bateman A, Sandford R . The PLAT domain: a new piece in the PKD1 puzzle . Curr. Biol. . 9 . 16 . R588–90. 1999 . 10469604 . 10.1016/S0960-9822(99)80380-7. 15018010 . free .
6. Ponting CP, Hofmann K, Bork P . A latrophilin/CL-1-like GPS domain in polycystin-1 . Curr. Biol. . 9 . 16 . R585–8 . August 1999 . 10469603 . 10.1016/S0960-9822(99)80379-0. 17252179 . free .