Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.13.3 (histidine kinase)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eukaryotic cellular proteins contain phosphohistidine. To search for protein histidine phosphatases, protein histidine kinase from Saccharomyces cerevisiae was used to phosphorylate histone H4 on histidine at position 75 in the H4 amino acid sequence. Incubation of the phosphorylated histone H4 with either protein phosphatase 1, 2A, or 2C resulted in extensive removal of phosphate from the phosphorylated histone. Thus, protein phosphatases 1, 2A, and 2C are histidine phosphatases as well as serine/threonine phosphatases. Calcium/calmodulin-regulated protein phosphatase (protein phosphatase 2B) did not remove phosphate from phosphohistidine. The histidine phosphatase reaction was tested for a magnesium requirement and effects of inhibitor-1 and okadaic acid. In all cases, the protein phosphatases behaved as they do in their serine/threonine phosphatase activity. Extracts of the yeast, S. cerevisiae, contain protein histidine phosphatase activity. Quantitative measurement of phosphatase activity shows that the activity against phosphohistidine is a major activity of protein phosphatases 1, 2A, and 2C.
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PMID:Protein phosphatases 1, 2A, and 2C are protein histidine phosphatases. 839 6

The multiple histidine-aspartate phosphorelay system plays a crucial role in cellular adaptation to environments in microorganisms and plants. Like kinase-phosphatase systems in higher eukaryotes, the multiple steps provide additional regulatory checkpoints with phosphatases. The Escherichia coli phosphatase SixA exhibits protein phosphatase activity against the histidine-containing phosphotransfer (HPt) domain located in the C-terminus of the histidine kinase ArcB engaged in anaerobic responses. We have determined the crystal structures of the free and tungstate-bound forms of SixA at 2.06 A and 1.90 A resolution, respectively. The results provide the first three-dimensional view of a bacterial protein histidine phosphatase, revealing a compact alpha/beta architecture related to a family of phosphatases containing the arginine-histidine-glycine (RHG) motif at their active sites. Compared with these RHG phosphatases, SixA lacks an extra alpha-helical subdomain as a lid over the active site, thereby forming a relatively shallow groove important for the accommodation of the HPt domain of ArcB. The tungstate ion, which mimics the substrate phosphate group, is located at the centre of the active site where the active residue, His8, points to the tungsten atom in the mode of in-line nucleophilic attack.
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PMID:Crystal structure of the protein histidine phosphatase SixA in the multistep His-Asp phosphorelay. 1567 Feb 9

Escherichia coli protein SixA was the first identified histidine protein phosphatase that dephosphorylates the histidine-containing phosphotransfer (HPt) domain of histidine kinase ArcB. The crystal structures of the free and tungstate-bound forms of SixA revealed an alpha/beta architecture with a fold unlike those previously described in eukaryotic protein phosphatases, but related to a family of phosphatases containing the arginine-histidine-glycine (RHG) motif at their active sites. Compared with these RHG phosphatases, SixA lacks an extra alpha-helical subdomain that forms a lid over the active site, thereby forming a relatively shallow groove important for accommodating the kidney-shaped four-helix bundle of the HPt domain. Sequence database searches revealed that a single SixA homolog was found in a variety of bacteria, where two homologs were found in some bacteria while no homolog was found in others. No SixA homologs were found in the majority of firmicutes and euryarchaea. Structure-based examination and multiple alignment of sequences revealed SixA active residues from loop beta1-H2, which might assist in the identification of SixA homologs among RHG phosphatases even with poor amino acid identity.
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PMID:Structure of SixA, a histidine protein phosphatase of the ArcB histidine-containing phosphotransfer domain in Escherichia coli. 1762 45