2wiu

Structural highlights

Function

[HIPA_ECOLI] Toxic component of a toxin-antitoxin (TA) module. Autophosphorylates (Ser-150) and phosphorylates EF-Tu in vitro (on 'Thr-383'), may act on other proteins as well. The hipA7 mutation leads to increased generation of persister cells, cells that survive antibiotic treatment probably by entering into a dormant state. Wild-type cells produce persisters at a frequency of 10-6 to 10-5 whereas mutant hipA7 cells produce persisters at a frequency of 10-2. Generation of persister cells requires (p)ppGpp as cells lacking relA or relA/spoT generate fewer or no persister cells respectively compared to hipA7. Low level expression of HipA causes cell filamentation and depending on the protein level is toxic enough to reduce cell growth or even kill cells. Expression of wild-type HipA also leads to high antibiotic tolerance of the survivor cells. The toxic effect of HipA is neutralized by its cognate antitoxin HipB. With HipB acts as a corepressor for transcription of the hipBA promoter.^{[1] [2] [3] [4] [5]} [HIPB_ECOLI] Antitoxin component of a toxin-antitoxin (TA) module. Neutralizes the toxic effect of cognate toxin HipA. Binds to operator sites with the consensus sequence 5-'TATCCN(8)GGATA-3' to repress the hipBA operon promoter.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Serine/threonine protein kinase 3D structures

References

1. ↑ Correia FF, D'Onofrio A, Rejtar T, Li L, Karger BL, Makarova K, Koonin EV, Lewis K. Kinase activity of overexpressed HipA is required for growth arrest and multidrug tolerance in Escherichia coli. J Bacteriol. 2006 Dec;188(24):8360-7. Epub 2006 Oct 13. PMID:17041039 doi:10.1128/JB.01237-06
2. ↑ Moyed HS, Bertrand KP. hipA, a newly recognized gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis. J Bacteriol. 1983 Aug;155(2):768-75. PMID:6348026
3. ↑ Black DS, Irwin B, Moyed HS. Autoregulation of hip, an operon that affects lethality due to inhibition of peptidoglycan or DNA synthesis. J Bacteriol. 1994 Jul;176(13):4081-91. PMID:8021189
4. ↑ Korch SB, Henderson TA, Hill TM. Characterization of the hipA7 allele of Escherichia coli and evidence that high persistence is governed by (p)ppGpp synthesis. Mol Microbiol. 2003 Nov;50(4):1199-213. PMID:14622409
5. ↑ Schumacher MA, Piro KM, Xu W, Hansen S, Lewis K, Brennan RG. Molecular mechanisms of HipA-mediated multidrug tolerance and its neutralization by HipB. Science. 2009 Jan 16;323(5912):396-401. PMID:19150849 doi:323/5912/396
6. ↑ Evdokimov A, Voznesensky I, Fennell K, Anderson M, Smith JF, Fisher DA. New kinase regulation mechanism found in HipBA: a bacterial persistence switch. Acta Crystallogr D Biol Crystallogr. 2009 Aug;65(Pt 8):875-9. Epub 2009, Jul 17. PMID:19622872 doi:10.1107/S0907444909018800