VapC-like PIN domain of Mycobacterium tuberculosis VapC11, VapC15, and related proteins
This subfamily includes the Virulence associated protein C (VapC)-like PIN (PilT N terminus) domain of Mycobacterium tuberculosis VapC11 and VapC15 toxins. M. tuberculosis VapC11 and VapC15 cleave tRNA3 Leu-CAG, VapC11 may additionally cleave tRNA13Leu-GAG and tRNA10Gln-CTG. This subgroup belongs to the VapC-like family of the PIN domain nuclease superfamily. VapC is a PIN-domain ribonuclease toxin from prokaryotic VapBC toxin-antitoxin (TA) systems. VapB is a transcription factor-like protein antitoxin acting as an inhibitor. Other members of the VapC-like nuclease family include FitB toxin of the FitAB TA system, eukaryotic ribonucleases such as Smg6, ribosome assembly factor NOB1, exosome subunit Rrp44 endoribonuclease and rRNA-processing protein Fcf1. The structural properties of the PIN 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 while some others 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.
Structure:4CHG; Mycobacterium tuberculosis VapB2C2-15 binds Mg2+ and Mn2+
Comment:the PIN domain active site comprises 4 or more negatively charged (Asp/Glu) residues, 3 of which are essentially invariant, and may be supplemented with additional Ser/Thr or Asn/Gln residues
Comment:based on Mycobacterium tuberculosis VapC15, M. tuberculosis VapC3, and related proteins with structure, and on experimental evidence
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