Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

In a French child with complete androgen insensitivity syndrome and negative receptor-binding, no gross deletion has been found. Using single-strand conformation polymorphism assay, a useful screening method for rapid detection of DNA sequence alterations, and direct DNA sequencing, a G-T nucleotide substitution in exon 5 of the androgen receptor gene at nucleotide 2590 was found. This changed codon 743, glycine to valine, in the hormone-binding domain and created a new recognition sequence for the restriction endonuclease Asp HI. Amplification of exon 5 by polymerase chain reaction followed by digestion with Asp HI enabled easy recognition of the described mutation. Since the mother's exon 5 was undigested, we suspected the de novo nature of this nucleotide substitution. This was confirmed by direct sequencing of the mother's DNA which only showed the canonical sequence. To our knowledge, there has been no previous report of a de novo mutation described within the androgen receptor gene in patients with androgen insensitivity syndrome.
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PMID:Complete androgen insensitivity syndrome associated with a de novo mutation of the androgen receptor gene detected by single strand conformation polymorphism. 809 90

The human immunodeficiency virus type 1 integrase protein can be specifically cross-linked to viral long terminal repeat substrate oligonucleotides in vitro by using UV light. Site-directed mutagenesis and deletion analyses were used to define the domains involved in the interaction of integrase with the viral DNA substrate. Our results showed that mutation of conserved residues Pro-109 and Asp-116, which are found to be critical for the endonuclease and integration activities of IN protein, abolished the ability of the protein to cross-link to its DNA substrate. Furthermore, deletion analysis experiments showed that removal of 39 amino acids from the amino terminus and deletion of 15 amino acids from the carboxyl terminus abolished DNA cross-linking.
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PMID:Conserved residues Pro-109 and Asp-116 are required for interaction of the human immunodeficiency virus type 1 integrase protein with its viral DNA substrate. 839 28

Escherichia coli RuvC protein is a specific endonuclease that resolves recombination intermediates into viable products. The structural features needed for RuvC activity were investigated by sequencing three ruvC mutations and relating the base pair changes identified to the activity of the mutant proteins. Each of the three mutations is a single base-pair substitution. ruvC51 converts glycine-15 to an aspartic acid residue. The product of ruvC51 was purified and shown to retain the ability to bind junctions, albeit with a slightly reduced affinity. However, it has lost the ability to resolve these structures by symmetrical cleavage. A multicopy ruvC51 plasmid confers sensitivity to UV light in a ruvC+ strain. The ruvC53 allele causes a glycine-17 to serine substitution while ruvC55 produces a stop codon. Neither of these genes produces a stable product. The results suggest that the N-terminal domain of RuvC may be concerned with cleavage of junctions.
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PMID:An E. coli RuvC mutant defective in cleavage of synthetic Holliday junctions. 839 86

We report a rare apolipoprotein E variant in an Irish female with Type III hyperlipidaemia who has the phenotype E2E1 as determined by isoelectric focusing. Sequence analysis of the apolipoprotein E gene from the proband and from four other family members, using DNA amplified by the polymerase chain reaction, demonstrated the presence of a point mutation in the common epsilon 2 allele with a G-->A transition at nucleotide 3791. This was confirmed by digestion with the restriction endonuclease TaqI, which cuts at a new site within the apolipoprotein E gene, created by the base change. This mutation results in a substitution of aspartic acid for glycine at position 127 of the mature protein. We believe this to be the first description of this apolipoprotein E variant in a family from the British Isles. The mutation appears to be 'recessive' with respect to the expression of Type III hyperlipidaemia, although it may be somewhat more potent in this regard than the parent epsilon 2 allele. The Type III hyperlipidaemia is responsive to treatment with diet and gemfibrozil.
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PMID:Rare apolipoprotein E variant identified in a patient with type III hyperlipidaemia. 850 53

Three novel point mutations were detected in the glucocerebrosidase gene of three unrelated Gaucher's disease patients by direct sequencing of PCR products. The first is a C to G change at position 4263 in the genomic sequence (exon 7) which results in a proline to arginine change at position 266 in the mature enzyme (P266R). The second is a G to C change at position 5276 in the genomic sequence (exon 8) which results in an aspartic acid to histidine change at position 315 (D315H). The third is a C to A change at position 5286 in the genomic sequence (exon 8) which results in an alanine to aspartic acid change at position 318 (A318D). The first mutation destroys an AvaII restriction endonuclease site, the second creates a BspMI site and the third creates a BamH I site.
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PMID:Three unrelated Gaucher's disease patients with three novel point mutations in the glucocerebrosidase gene (P266R, D315H and A318D). 854 70

The phenotypic characteristics of isolated growth hormone deficiency (IGHD) type IB in humans, such as autosomal recessive inheritance, time of onset of growth retardation, diminished secretion of growth hormone (GH) and IGF-I, proportional reduction in weight and size, and delay in sexual maturation, has much in common with the phenotype of the homozygous little/little (lit/lit) mouse. Sequencing of the GH releasing hormone (GHRH) receptor in lit/lit mice has shown a single nucleotide substitution within the extracellular peptide binding domain at codon 60 that changed aspartic acid to glycine. Therefore, the GHRH receptor is a reasonable candidate gene for causing IGHD in humans. DNA from 65 unrelated healthy Caucasians of normal stature and 65 children with IGHD type IB of whom 12 did not respond to exogenous treatment with GHRH were studied. Restriction endonuclease analysis, linkage studies, and polymerase chain reaction amplification and sequencing of the whole extracellular domain including the first three membrane spanning domains of the GHRH receptor gene were performed. None of the analyses revealed any structural abnormalities in these patients with IGHD. This suggests that a lit/lit mouse equivalent is an unlikely explanation for the majority of children with IGHD. Although gross structural abnormalities in the whole gene have been ruled out in this study, mutations in the carboxyl terminus are still possible, and, therefore, the remaining part of the gene needs to be sequenced.
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PMID:Isolated growth hormone deficiency: testing the little mouse hypothesis in man and exclusion of mutations within the extracellular domain of the growth hormone-releasing hormone receptor. 861 1

The amino acid Asp-59 was proposed to be involved in EcoRI catalyzed DNA cleavage (Cheng et al., EMBO J. 13, 3927-35, 1994). We have tested this hypothesis by site directed mutagenesis experiments. The four mutants D59A, D59E, D59G, and D59N bind with similar stability to the specific recognition sequence as wild type EcoRI. The D59E mutant cleaves DNA as fast as the wild type enzyme. Specific activities of the other three mutants are five to tenfold lower. Therefore, we conclude that Asp-59 is not involved in catalysis of the EcoRI restriction endonuclease. Consequences for catalytic mechanisms of EcoRI and other restriction enzymes are discussed.
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PMID:Asp-59 is not important for the catalytic activity of the restriction endonuclease EcoRI. 864 14

Phosphatidylcholine-specific phospholipase D (PLD) enzymes catalyze hydrolysis of phospholipid phosphodiester bonds, and also transphosphatidylation of phospholipids to acceptor alcohols. Bacterial and plant PLD enzymes have not been shown previously to be homologues or to be homologous to any other protein. Here we show, using sequence analysis methods, that bacterial and plant PLDs show significant sequence similarities both to each other, and to two other classes of phospholipid-specific enzymes, bacterial cardiolipin synthases, and eukaryotic and bacterial phosphatidylserine synthases, indicating that these enzymes form an homologous family. This family is suggested also to include two Poxviridae proteins of unknown function (p37K and protein K4), a bacterial endonuclease (nuc), an Escherichia coli putative protein (o338) containing an N-terminal domain showing similarities with helicase motifs V and VI, and a Synechocystis sp. putative protein with a C-terminal domain likely to possess a DNA-binding function. Surprisingly, four regions of sequence similarity that occur once in nuc and o338, appear twice in all other homologues, indicating that the latter molecules are bi-lobed, having evolved from an ancestor or ancestors that underwent a gene duplication and fusion event. It is suggested that, for each of these enzymes, conserved histidine, lysine, aspartic acid, and/or asparagine residues may be involved in a two-step ping pong mechanism involving an enzyme-substrate intermediate.
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PMID:A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identification of duplicated repeats and potential active site residues. 873 63

Hepatic angiosarcoma (HA) is an uncommon neoplasm associated with known etiologic factors in 25% to 42% of cases. It is, however, one of the most common sarcomas found in the liver. The aim of this study was to find was to find mutations in the K-ras-2 oncogene in sporadic and Thorotrast (TT)-induced HA. Point mutations in K-ras-2 were sought in archival, formalin-fixed tissue blocks from 24 patients with angiosarcoma. Of these, 19 cases were sporadic and 5 were TT-induced. Mutational analysis was performed by topographic microdissection with PCR amplification followed by genotyping. Specific mutations were determined by two independent methods: (a) direct sequencing of the PCR product confirmed by rePCR and by using a different sequencing primer, and (b) PCR-based selective enrichment of mutant DNA by endonuclease digestion followed by heteroduplex DNA analysis using denaturing gradient gel electrophoresis. Eleven K-ras-2 point mutations were detected in 7 of 24 (29%) tumors, including 5 of 19 (26%) sporadic HA and 2 of 5 (40%) TT-induced HA. There were seven G:C > A:T and four G:C > T:A mutations. All seven mutated tumors contained a codon 12-aspartate amino acid substitution. In addition, a second codon 12-cysteine mutant cell population was present in one of two codon 12-aspartate mutated TT-induced HA and in three of five codon 12-aspartate sporadic tumors. Of these four tumors, three contained both aspartate and cysteine mutations and were composed of multiple nodules; the fourth was a single mass. Seventeen tumors had multiple nodules; whereas 5 had a K-ras-2 mutation, 12 were wild-type. The molecular pathology of both sporadic and TT-induced HA is characterized by a high rate of K-ras-2 mutations characteristic of oxidative damage (ie, G:C > A:T and G:C > T:A mutations) resulting in two mutated population sets: codon 12 GGT > GAT and GGT > TGT (glycine to aspartic acid and cysteine). This is, to date, the first study to characterize the K-ras-2 gene mutations within human sporadic and TT-induced HA by direct sequence analysis and denaturing gradient gel electrophoresis. These data further support the hypothesis linking adduct-forming vinyl chloride exposure to HA containing a much higher frequency of K-ras-2 mutations and a mutational spectrum characteristic of chloroethylene oxide, a carcinogenic metabolite of vinyl chloride.
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PMID:Sporadic and Thorotrast-induced angiosarcomas of the liver manifest frequent and multiple point mutations in K-ras-2. 901 Apr 58

XPG is a member of the FEN-1 structure-specific endonuclease family. It has 3'-junction cutting activity on bubble substrates and makes the 3'-incision in the human dual incision (excision nuclease) repair system. To investigate the precise role of XPG in nucleotide excision repair, we mutagenized two amino acid residues thought to be involved in DNA binding and catalysis, overproduced the mutant proteins using a baculovirus/insect cell system, and purified and characterized the mutant proteins. The mutation D77A had a modest effect on junction cutting and excision activity and gave rise to uncoupled 5'-incision by mammalian cell-free extracts. The D812A mutation completely abolished the junction cutting and 3'-incision activities of XPG, but the excision nuclease reconstituted with XPG (D812A) carried out normal 5'-incision at the 23rd-24th phosphodiester bonds 5' to a (6-4) photoproduct without producing any 3'-incision. It is concluded that Asp-812 is an active site residue of XPG and that in addition to making the 3'-incision, the physical presence of XPG in the protein-DNA complex is required non-catalytically for subsequent 5'-incision by XPF-ERCC1.
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PMID:The non-catalytic function of XPG protein during dual incision in human nucleotide excision repair. 918 7


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