New kinase regulation mechanism found in HipBA: a bacterial persistence switch.
Bacterial persistence is the ability of individual cells to randomly enter a period of dormancy during which the cells are protected against antibiotics. In Escherichia coli, persistence is regulated by the activity of a protein kinase HipA and its DNA-binding partner HipB, which is a strong inhibitor of both HipA activity and hip operon transcription. The crystal structure of the HipBA complex was solved by application of the SAD technique to a mercury derivative. In this article, the fortuitous and interesting effect of mercury soaks on the native HipBA crystals is discussed as well as the intriguing tryptophan-binding pocket found on the HipA surface. A HipA-regulation model is also proposed that is consistent with the available structural and biochemical data.
Evdokimov
Artem
A
Pfizer Inc, Groton, Connecticut, USA. artem@xtals.org
Voznesensky
Igor
I
Fennell
Kimberly
K
Anderson
Marie
M
Smith
James F
JF
Fisher
Douglas A
DA
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000201:enzymology*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005812:Genes, Switch / Q000235:genetics; D006801:Humans; D008628:Mercury / Q000378:metabolism; D009876:Operon; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D047428:Protein Kinase Inhibitors; C070740:hipB protein, E coli; C070741:hipA protein, E coli; D014364:Tryptophan; D008628:Mercury