type II toxin-antitoxin sytem toxin HipA from Escherichia coli and similar proteins
This family contains type II toxin-antitoxin (TA) system HipA family toxins similar to Escherichia coli HipA, a serine/threonine-protein kinase that phosphorylates Glu-tRNA-ligase (GltX), preventing it from being charged, leading to an increase in uncharged tRNA(Glu). This induces amino acid starvation and the stringent response via RelA/SpoT and increased (p)ppGpp levels, which inhibits replication, transcription, translation and cell wall synthesis, reducing growth and leading to persistence and multidrug resistance. HipA is the toxin component of the HipA-HipB TA module that is a major factor in persistence and bioflim formation; its toxic effect is neutralized by its cognate antitoxin HipB. HipA, with HipB, acts as a a corepressor for transcription of the hipBA promoter. In the Escherichia coli HipAB:DNA promoter complex, HipA forms a dimer and each HipA monomer interacts with a HipB homodimer which binds DNA. The HipAB component of the complex is composed of two HipA and four HipB subunits.