Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pseudomonas aeruginosa was recently found to possess a cluster of structural genes encoding phenylalanine hydroxylase (PhhA), carbinolamine dehydratase (PhhB), and aromatic aminotransferase (PhhC). We now report the presence, in the flanking upstream region, of a divergently transcribed gene (phhR) encoding an activator protein. Inactivation of phhR markedly reduced expression of the structural genes. PhhR belongs to the large prokaryote family of sigma 54 enhancer-binding proteins, and activation of the phh operon by PhhR in P. aeruginosa required rpoN. The closest homologues of PhhR are the TyrR proteins from Escherichia coli and Haemophilus influenzae. E. coli TyrR is an unusual member of the homologue family in that the transcriptional units regulated by tyrR are driven by sigma 70 promoters. P. aeruginosa phhR was able to replace E. coli tyrR as a repressor of the aroF-tyrA operon (but not as an activator of mtr) in the heterologous E. coli system. Two regions that resemble E. coli TyrR boxes were identified in the intervening region between phhR and phhA. We propose that one or both boxes may be the target of PhhR acting as an autogenous repressor at a sigma 70 promoter in one direction. In the other direction, one or both boxes may be the upstream activator sequence targeted by PhhR to facilitate expression of the phh operon from a sigma 54 promoter. The phh operon was strongly induced in fructose- or glucose-based minimal medium by L-phenylalanine. Inactivation of phhR in P. aeruginosa abolished ability to utilize either L-phenylalanine or L-tyrosine as a sole source of carbon for growth.
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PMID:PhhR, a divergently transcribed activator of the phenylalanine hydroxylase gene cluster of Pseudomonas aeruginosa. 893 33

Highly purified preparations of the TyrR protein of Haemophilus influenzae Rd undergo specific and limited proteolytic cleavage during storage at 4 degreesC to generate two fragments of 28 and 8 kDa. Under nondenaturing conditions, the two fragments remain tightly associated. Nicked TyrR is identical to full-length TyrR in its operator binding characteristics. The 8-kDa fragment containing amino acid residues 258-318 was separated from the 28-kDa fragment (residues 1-257) by gel filtration chromatography in the presence of 4 M urea. Upon renaturation, this fragment bound to operator with an affinity similar to that of full-length TyrR but was unresponsive to ligands that normally modulate operator binding (gamma-S-ATP and L-tyrosine). It was not possible to renature the urea-treated 28-kDa fragment. Highly purified soluble preparations of truncated TyrR containing residues 1-257 were obtained after the overexpression of a shortened form of the tyrR gene via a specific plasmid construct. By several criteria, this species had native secondary and tertiary structure. The 28-kDa fragment was unable to bind to operator but could reconstitute nicked TyrR when added to the renatured 8-kDa fragment, as shown by physical properties and responsiveness to cofactors in operator binding. When either the 28- or 8-kDa species was expressed in vivo, there was no detectable operator binding, as evaluated using a lacZ reporter system driven by the repressible aroF promoter. When the two fragments were co-expressed in a common cytoplasm, an operator-binding species was formed, as demonstrated through partial restoration of repression capability.
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PMID:Isolated operator binding and ligand response domains of the TyrR protein of Haemophilus influenzae associate to reconstitute functional repressor. 988 May 68

The TyrR protein of Escherichia coli (513 amino acid residues) is the chief transcriptional regulator of a group of genes that are essential for aromatic amino acid biosynthesis and transport. The TyrR protein can function either as a repressor or as an activator. The central region of the TyrR protein (residues 207 to 425) is similar to corresponding polypeptide segments of the NtrC protein superfamily. Like the NtrC protein, TyrR has intrinsic ATPase activity. Here, we report that TyrR possesses phosphatase activity. This activity is subject to inhibition by L-tyrosine and its analogues and by ATP and ATP analogues. Zinc ion (2 mM) stimulated the phosphatase activity of the TyrR protein by a factor of 57. The phosphatase-active site of TyrR was localized to a 31-kDa domain (residues 191 to 467) of the protein. However, mutational alteration of distant amino acid residues at both the N terminus and the C terminus of TyrR altered the phosphatase activity. Haemophilus influenzae TyrR (318 amino acid residues), a protein with a high degree of sequence similarity to the C terminus of the E. coli TyrR protein, exhibited a phosphatase activity similar to that of E. coli TyrR.
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PMID:The sigma(70) transcription factor TyrR has zinc-stimulated phosphatase activity that is inhibited by ATP and tyrosine. 1064 32