Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microcytic red cells from a 70 year old Negro man with mild anemia contained only hemoglobin G-Philadelphia. Red cells from all of his children had low-normal MCV's, and contained 32-34 percent of the abnormal hemoglobin. Oxygen affinity of his blood and stability of his hemolysate were normal, suggesting that his mild anemia was not caused by the the abnormal hemoglobin. Restriction endonuclease analyses of DNA from the proband and his offspring showed that the alpha G-Philadelphia globin gene exists in only one copy per chromosome. The new gene was probably created by an unequal cross-over which deleted an alpha globin coding sequence (derived from one or both alpha globin genes), as well as some or all of the DNA sequence between those genes.
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PMID:Homozygous alpha thalassemia/Hb G Philadelphia. 629 2

In humans the alpha-globin genes are duplicated and closely linked. Whereas individuals heterozygous for most alpha-chain mutations possess approximately 25% abnormal hemoglobin, heterozygotes for the alpha-chain variant Hb G Philadelphia synthesize either 33% or 50% Hb G. Both variable gene dosage and interaction with alpha-thalassemia have been proposed to explain this observation. To differentiate between these models, we have performed restriction endonuclease mapping and hematological studies on individuals with Hb G from four families. In every case the alpha G locus was carried on an EcoRI or EcoRI + BamHI fragment approximately 4 kilobases shorter than that bearing the two linked alpha A loci of hematologically normal individuals. Bgl II digestion revealed that the alpha G gene is the only alpha locus on the affected chromosome. Erythrocyte indices and alpha/beta synthesis ratios indicated that the alpha G chromosome confers alpha-thalassemia. In addition to the alpha G gene, subjects who synthesized 33% Hb G possessed two alpha A genes on the homologous chromosome and exhibited the mild form of alpha-thalassemia trait ("silent carrier"). Subjects who synthesized 50% Hb G possessed a single alpha A gene trans to the alpha G locus and displayed the more pronounced form of alpha-thalassemia trait. One subject, who synthesized 100% alpha G chains and had Hb G-Hb H disease, was found to have a single nonfunctional alpha gene trans to the alpha G gene. Thus the proportion of Hb G synthesized by heterozygotes is determined by interaction with alpha-globin gene deletions cis and trans to the alpha G locus.
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PMID:Proportion of hemoglobin G Philadelphia (alpha 268 Asn leads to Lys beta 2) in heterozygotes is determined by alpha-globin gene deletions. 693 89

Hemoglobin (Hb) M-Saskatoon, a beta variant of methemoglobin, is characterized by mild hemolysis. It is caused by the substitution of a histidine by a tyrosine at the 63rd amino acid residue of the beta-globin chain. Amplification and sequence analysis of genomic beta-globin DNA from an Indonesian boy diagnosed as having the more severe disease thalassemia demonstrated the presence of a C to T transition at nucleotide 473 in one of the two beta-globin genes resulting in a histidine to tyrosine substitution at 63rd residue. This amino acid change matched with that reported in Hb M-Saskatoon. This nucleotide change abolished a recognition site for the restriction endonuclease NlaIII. NlaIII digestion of the corresponding beta-globin DNA amplified from the patient's parents indicated that the mutation was inherited through from his mother. This result shows that the world-wide distribution of Hb M-Saskatoon extends to Indonesia, where it was not previously identified. Possible causes of the unusually severe symptoms observed in the case are discussed.
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PMID:C to T transition at the first nucleotide of codon 63 of the beta-globin gene corresponding to hemoglobin M-Saskatoon in an Indonesian boy. 766

Hb Kurosaki [alpha 7(A5)Lys --> Glu (AAG --> GAG)], has been found for the first time in Thailand. The 30-year-old Thai male had a normal hematological profile at the steady state, but showed an abnormal hemoglobin (Hb) present at a level of 28%. Protein characterization was performed by automated sequencer analysis of the abnormal alpha-globin chain and amino acid analysis of the abnormal alphaT-1,2 peptide. Direct DNA sequence analysis of selectively amplified segments of the alpha1 and alpha2 genes showed that codon 7 of the alpha2-globin gene was heterozygous for AAG (Lys) and GAG (Glu). This was confirmed by restriction endonuclease digestion with Eco31I.
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PMID:Hb Kurosaki [alpha7(A5)Lys -->Glu (AAG --> GAG)]: an alpha2-globin gene mutation found in Thailand. 1592 Nov 68

Heme proteins, metmyoglobin, methemoglobin, and metcytochrome c showed unusual affinity for double-stranded DNA. Calorimetric studies show that binding of methemoglobin to calf thymus DNA (CTDNA) is weakly endothermic, and the binding constant is 4.9+/-0.7x10(5) M(-1). The Soret absorption bands of the heme proteins remained unchanged, in the presence of excess CTDNA, but a new circular dichroic band appeared at 210 nm. Helix melting studies indicated that the protein-DNA mixture denatures at a lower temperature than the individual components. Thermograms obtained by differential scanning calorimetry of the mixture indicated two distinct transitions, which are comparable to the thermograms obtained for individual components, but there was a reduction in the excess heat capacity. Activation of heme proteins by hydrogen peroxide resulted in the formation of high valent Fe(IV) oxo intermediates, and CTDNA reacted rapidly under these conditions. The rate was first-order in DNA concentration, and this reactivity resulted in DNA strand cleavage. Upon activation with hydrogen peroxide, for example, the heme proteins converted the supercoiled pUC18 DNA into nicked circular and linear DNA. No reaction occurred in the absence of the heme protein, or hydrogen peroxide. These data clearly indicate a novel property of several heme proteins, and this is first report of the endonuclease-like activity of the heme proteins.
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PMID:Endonuclease-like activity of heme proteins. 1620 93