PROSITE documentation PDOC51898

Tyrosine recombinase domains profiles

Tyrosine-type site-specific recombinases are ubiquitous in eubacteria, prevalent in archaea and temperate phages and present in certain yeast strains. They catalyze a variety of sequence-specific DNA rearrangements in biological systems, including the integration and excision of phage genomes into and out of their bacterial hosts, conjugative transposition, resolution of catenated DNA circles, regulation of plasmid copy number, DNA excision to control gene expression for nitrogen fixation in Anabaena and DNA inversions controlling expression of cell surface proteins or DNA replication. Well studied members of the family include the phage lambda integrase, responsible for integration of the lambda phage genome, the phage P1 recombinase, involved in cyclization of the P1 genome as well as resolution of genomic multimers, the Escherichia coli XerC/XerD recombinases, responsible for resolution of dimers of the bacterial chromosome, and the yeast Flp recombinase, responsible for the control of plasmid copy number. Tyrosine recombinase family members have the distinctive ability to carry out a complete site-specific recombination reaction between two DNAs in the absence of high energy cofactors. DNA cleavage and rejoining is accomplished in two steps. First, a tyrosine hydroxyl attacks the scissile phosphate, nicking the DNA and forming a 3' phosphotyrosine-linked DNA complex. This covalent protein-DNA intermediate is resolved when the 5' terminal hydroxyl of the invading DNA strand attacks the phosphotyrosine linkage and displaces the protein, forming a holliday junction. The reaction is repeated for the other strand of each DNA partner, generating the recombinant DNA duplexes. It is the transient covalent linkage of protein and DNA that conserves the energy of the broken phosphodiester bond, enabling a pair of reciprocal strand exchanges to proceed [1,2,3,4,5].

The tyrosine recombinase catalytic domain spans ~180 amino acids and its active site is composed of seven conserved residues: two arginine and histidine residues, an aspartate or glutamate, a lysine and the essential catalytic tyrosine residue. These residues play catalytic roles in several enzymes. Specifically the Tyr and Lys serves as nucleophile and general acid catalysts, respectively. The two Arg residues neutralize the negative charge during the transition state and activate the scissile phosphate by the catalytic tyrosine residue. Finally, the two His and the Glu/Asp residues stabilize the transition state [2,6]. The core tyrosine recombinase catalytic domain has a mixed α-β structure consisting of seven α helices and seven β strands (see <PDB:<1AE9>). An α-helical bundle with an unusual packing geometry is cradled by two antiparallel β hairpins [7]. The yeast Flp tyrosine recombinase domain contains an additional C-terminal extension not found in the core tyrosine recombinase domain of archaea, prokaryotes and phages (see <PDB:1FLO>). This extension forms a β hairpin and three short helices that pack onto the opposite face of the tyrosine recombinase core domain from the DNA [8].

We developed two profiles for tyrosine recombinase domains. The first one covers the entire core domain of prokaryotes, archaea and phages, whereas the second covers the entire tyrosine recombinase domain of yeast, including its C-terminal extension.