Abstract
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.
MeSH terms
-
Anti-Bacterial Agents / therapeutic use
-
Binding Sites
-
Crystallization
-
Crystallography, X-Ray
-
DNA-Binding Proteins / chemistry*
-
DNA-Binding Proteins / metabolism
-
Drug Resistance, Bacterial
-
Escherichia coli / enzymology*
-
Escherichia coli Infections / drug therapy
-
Escherichia coli Infections / metabolism
-
Escherichia coli Infections / microbiology
-
Escherichia coli Proteins / chemistry*
-
Escherichia coli Proteins / metabolism
-
Gene Expression Regulation, Bacterial
-
Genes, Switch / genetics
-
Humans
-
Mercury / metabolism
-
Operon
-
Protein Conformation
-
Protein Kinase Inhibitors / chemistry*
-
Protein Kinase Inhibitors / metabolism
-
Structure-Activity Relationship
-
Tryptophan / metabolism
Substances
-
Anti-Bacterial Agents
-
DNA-Binding Proteins
-
Escherichia coli Proteins
-
Protein Kinase Inhibitors
-
hipB protein, E coli
-
hipA protein, E coli
-
Tryptophan
-
Mercury