VapC-like PIN domain of Neisseria gonorrhoeae FitB and related proteins
This subfamily includes the Virulence associated protein C (VapC)-like PIN (PilT N terminus) domain of Neisseria gonorrhoeae FitB toxin of the FitAB toxin/antitoxin (TA) system. This subfamily belongs to the VapC-like family of the PIN domain nuclease superfamily. VapC is the PIN-domain ribonuclease toxin from prokaryotic VapBC toxin-antitoxin (TA) systems. VapB is a transcription factor-like protein antitoxin acting as an inhibitor. In N. gonorrhoeae, FitA and FitB form a heterodimer: FitA is the DNA binding subunit and FitB contains a ribonuclease activity that is blocked by the presence of FitA. A tetramer of FitAB heterodimers binds DNA from the fitAB upstream promoter region with high affinity. This results in both sequestration of FitAB and repression of fitAB transcription. It is thought that FitAB release from the DNA and subsequent dissociation both slows N. gonorrhoeae replication and transcytosis by an as yet undefined mechanism. The toxin M. tuberculosis VapC is a structural homolog of N. gonorrhoeae FitB, but their antitoxin partners, VapB and FitA, respectively, differ structurally. The structural properties of the PIN (PilT N terminus) domain indicate its active center, consisting of three highly conserved catalytic residues which coordinate metal ions, in some members, additional metal coordinating residues can be found. Some members of the superfamily lack several of these key catalytic residues. The PIN active site is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.
Comment:based on homology with related nucleases with structure including VapC toxin from Shigella flexneri 2a virulence plasmid pMYSH6000 and on experimental evidence
Comment:The PIN domain superfamily contains three highly conserved catalytic residues which coordinate metal ions; in some members, additional metal coordinating residues can be found while some others lack several of these key catalytic residues.
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