PROSITE documentation PDOC00865

Thermonuclease domain signatures and profile

Staphylococcus aureus secretes a thermostable nuclease (EC 3.1.31.1), known as thermonuclease (TNase) or staphylococcal nuclease (SNase), which is a calcium-dependent enzyme that catalyzes the hydrolysis of both DNA and RNA at the 5' position of the phosphodiester bond yielding 3'-mononucleotides and dinucleotides [1]. Three residues, two arginines and a glutamate, have been implicated in the catalytic mechanism.

The sequence of the TNase of S.aureus is evolutionary related [2,3,4] to that of other Staphylococcus as well as to:

  - Nuclease from the pSa plasmid of Shigella flexneri.
  - Escherichia  coli  plasmid RP4 parB protein, which is involved in  plasmid
    partition.
  - Escherichia coli plasmid R100 hypothetical protein (OrfA).
  - Rhizobium meliloti succinoglycan biosynthesis protein exoI.
  - Bacillus subtilis hypothetical protein yhcR.
  - Mycoplasma genitalium hypothetical lipoprotein MG186.
  - Haemophilus influenzae hypothetical protein HI1296.
  - Methanococcus jannaschii hypothetical protein MJ1439.
  - Yeast hypothetical protein Ygl085w.
  - A   38.1   Kd  protein  of  unknown  function  from  the  plant  Corydalis
    sempervirens.
  - Human  Epstein-Barr  virus  nuclear  antigen  2 (EBNA-2) coactivator p100,
    which contains  four repeats homologous to TNase. As each of these repeats
    lacks equivalent  TNase  catalytic  residues, they are unlikely to possess
    TNase-like activities,   but   may   mediate  single-stranded  DNA-binding
    function.
  - Caenorhabditis elegans F10g7.2 protein, which is similar to the human p100
    coactivator.

The TNase-like domain is about 150 residues long and consists of a highly twisted five stranded β-barrel and three helices. It folds into two subdomains consisting of an oligonucleotide/oligosaccharide-binding (OB)-fold and two C-terminal helices. The OB-fold consists of a five-stranded Greek-key β-barrel often capped by an α-helix located between the third and fourth strands. It is found in several proteins that bind nucleic acid as well as carbohydrates, whereas others bind protein receptors or small molecules [4].

We developed two signature patterns based on conserved regions that each contain active site residues. We also developed a profile that spans the entire TNase-like domain.