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Archives of Internal Medicine, 1978
A 52-year-old man had aregenerative anemia unresponsive to pyridoxine hydrochloride. Acute leukem... more A 52-year-old man had aregenerative anemia unresponsive to pyridoxine hydrochloride. Acute leukemia developed, and he died four months after diagnosis. At autopsy he had acute megakaryocytic leukemia with involvement of bone marrow, liver, spleen, adrenals, kidneys, and thyroid. Chromosomal analysis revealed absence of both diploid and Ph1 chromosomes. A mode of 45 chromosomes and aneuploidy were present. This is similar to the only other case with chromosomal studies. Of the 15 acceptable documented cases, eight were men and seven were women. Their age varied from 28 to 76 (mean, 55) years. Only two were less than 40 years of age. Most had pancytopenia, and all were dead within six months of diagnosis.
European Journal of Biochemistry, 1988
The bifunctional P protein (chorismate mutase : prephenate dehydratase) from Acinetobacter calcoa... more The bifunctional P protein (chorismate mutase : prephenate dehydratase) from Acinetobacter calcoaceticus has been purified. It was homogeneous in polyacrylamide gels and was more than 95% pure on the basis of the immunostaining of purified P protein with the antibodies raised against the P protein. The native enzyme is a homodimer (M , = 91 000) composed of 45-kDa subunits. A twofold increase in the native molecular mass of the P protein occurred in the presence of L-phenylalanine (inhibitor of both activities) or L-tyrosine (activator of the dehydratase activity) during gel filtration. Chorismate mutase activity followed Michaelis-Menten kinetics with a K,,, of 0.55 mM for chorismate. L-Phenylalanine was a relatively poor non-competitive inhibitor of the mutase activity. The chorismate mutase activity was also competitively inhibited by prephenate (reaction product). Substrate-saturation curves for the dehydratase activity were sigmoidal showing positive cooperativity among the prephenate-binding sites. L-Tyrosine activated prephenate dehydratase strongly but did not abolish positive cooperativity with respect to prephenate. L-Phenylalanine inhibited the dehydratase activity, and the substrate-saturation curves became increasingly sigmoidal as phenylalanine concentrations were increased with happ values changing from 2.0 (no phenylalanine) to 4.0 (0.08 mM L-phenylalanine). A sigmoidal inhibition curve of the dehydratase activity by L-phenylalanine gave Hill plots having a slope of-2.9. Higher ionic strength increased the dehydratase activity by reducing the positive cooperative binding of prephenate, and the sigmoidal substrate-saturation curves were changed to nearhyperbolic form. The happ values decreased with increase in ionic strength. Antibodies raised against the purified P protein showed cross-reactivity with the P proteins from near phylogenetic relatives of A. calcoaceticus. At a greater phylogenetic distance, cross-reaction was superior with P protein from Neisseria gonorrhaeae than with that from the more closely related Escherichia coli. Multifunctional proteins having more than one catalytic center have been studied in great detail and continue to intrigue biochemists. Typically, exhaustive information exists for one organism, often Escherichia coli, but there is little or no information about their phylogenetic distribution [l]. A few good examples are the two bifunctional aspartokinase : homoserine dehydrogenase enzymes and the two bifunctional proteins participating in tryptophan biosynthesis [2-41. In prokaryotes the evolutionary origins of two bifunctional proteins that function in phenylalanine and tyrosine biosynthesis have been pinpointed [ 5 ]. These are the P protein (chorismate mutase : prephenate dehydratase) of phenylalanine biosynthesis and the T protein (chorismate mutase : cyclohexadienyl dehydrogenase) of tyrosine biosynthesis. The P protein evolved earliest while the T protein is of much more recent origin [6]. Roughly 70% of all gram-negative bacteria possess the P protein, while only a small subcluster (enteric bacteria) additionally possesses the T protein.
Archives of Internal Medicine, 1978
A 52-year-old man had aregenerative anemia unresponsive to pyridoxine hydrochloride. Acute leukem... more A 52-year-old man had aregenerative anemia unresponsive to pyridoxine hydrochloride. Acute leukemia developed, and he died four months after diagnosis. At autopsy he had acute megakaryocytic leukemia with involvement of bone marrow, liver, spleen, adrenals, kidneys, and thyroid. Chromosomal analysis revealed absence of both diploid and Ph1 chromosomes. A mode of 45 chromosomes and aneuploidy were present. This is similar to the only other case with chromosomal studies. Of the 15 acceptable documented cases, eight were men and seven were women. Their age varied from 28 to 76 (mean, 55) years. Only two were less than 40 years of age. Most had pancytopenia, and all were dead within six months of diagnosis.
European Journal of Biochemistry, 1988
The bifunctional P protein (chorismate mutase : prephenate dehydratase) from Acinetobacter calcoa... more The bifunctional P protein (chorismate mutase : prephenate dehydratase) from Acinetobacter calcoaceticus has been purified. It was homogeneous in polyacrylamide gels and was more than 95% pure on the basis of the immunostaining of purified P protein with the antibodies raised against the P protein. The native enzyme is a homodimer (M , = 91 000) composed of 45-kDa subunits. A twofold increase in the native molecular mass of the P protein occurred in the presence of L-phenylalanine (inhibitor of both activities) or L-tyrosine (activator of the dehydratase activity) during gel filtration. Chorismate mutase activity followed Michaelis-Menten kinetics with a K,,, of 0.55 mM for chorismate. L-Phenylalanine was a relatively poor non-competitive inhibitor of the mutase activity. The chorismate mutase activity was also competitively inhibited by prephenate (reaction product). Substrate-saturation curves for the dehydratase activity were sigmoidal showing positive cooperativity among the prephenate-binding sites. L-Tyrosine activated prephenate dehydratase strongly but did not abolish positive cooperativity with respect to prephenate. L-Phenylalanine inhibited the dehydratase activity, and the substrate-saturation curves became increasingly sigmoidal as phenylalanine concentrations were increased with happ values changing from 2.0 (no phenylalanine) to 4.0 (0.08 mM L-phenylalanine). A sigmoidal inhibition curve of the dehydratase activity by L-phenylalanine gave Hill plots having a slope of-2.9. Higher ionic strength increased the dehydratase activity by reducing the positive cooperative binding of prephenate, and the sigmoidal substrate-saturation curves were changed to nearhyperbolic form. The happ values decreased with increase in ionic strength. Antibodies raised against the purified P protein showed cross-reactivity with the P proteins from near phylogenetic relatives of A. calcoaceticus. At a greater phylogenetic distance, cross-reaction was superior with P protein from Neisseria gonorrhaeae than with that from the more closely related Escherichia coli. Multifunctional proteins having more than one catalytic center have been studied in great detail and continue to intrigue biochemists. Typically, exhaustive information exists for one organism, often Escherichia coli, but there is little or no information about their phylogenetic distribution [l]. A few good examples are the two bifunctional aspartokinase : homoserine dehydrogenase enzymes and the two bifunctional proteins participating in tryptophan biosynthesis [2-41. In prokaryotes the evolutionary origins of two bifunctional proteins that function in phenylalanine and tyrosine biosynthesis have been pinpointed [ 5 ]. These are the P protein (chorismate mutase : prephenate dehydratase) of phenylalanine biosynthesis and the T protein (chorismate mutase : cyclohexadienyl dehydrogenase) of tyrosine biosynthesis. The P protein evolved earliest while the T protein is of much more recent origin [6]. Roughly 70% of all gram-negative bacteria possess the P protein, while only a small subcluster (enteric bacteria) additionally possesses the T protein.