Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

deltaHm, deltaT, Tm of melting of polydesoxyribonucletides polydAdT,, polyd(A--T)d(A--T), polyd(A--C)d(T--G) and DNA with different basic composition in a wide range of (10-2--4.0 M) ions (C2H5)4N+, Cs+ and Na+ were determined by the method microcalorimetry. It was established that the difference in melting heats of deltaHpolydAdT--deltaHpolyd(A--T)d(A--T) being approximately 0.6 kcal/mol b. p. represents that part of the energy which is caused by the heterogeneity of Stacking of interaction between (formula: see text) pairs. It is shown that the narrowing of deltaTm with increasing DNA concentration is connected with the decrease of the difference of polyGC and poly AT melting temperatures, what is with the parameter TGC--TAT which characterizes the melting of a free macromolecule.
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PMID:[Thermal properties of DNA and polydeoxyribonucleotides in a wide range of ionic concentration of neutral salts and a polymer]. 91 26

In four abnormal fibrinogens with a point mutation in the gamma chain, all characterized by impaired fibrin polymerization, we identified single base exchanges in the respective mutant gamma chain genes by polymerase chain reaction followed by DNA sequence analysis. These base exchanges accounted for the amino acid substitutions previously reported from our laboratory. They were exchanges of C to T (CGC for gamma Arg-275 to TGC for Cys) in fibrinogen Osaka II, T to G (AAT for gamma Asn-308 to AAG for Lys) in fibrinogen Kyoto I, T to C (ATG for gamma Met-310 to ACG for Thr) in fibrinogen Asahi, and G to T (GAT for gamma Asp-330 to TAT for Tyr) in fibrinogen Kyoto III. These base exchanges were found to reside in exon VIII of the gamma chain gene. Since many abnormal molecules are associated with polymerization defects, unless associated with the impaired release of fibrinopeptides A and/or B, exon VIII of the gamma chain gene may deserve careful study to define the structural alterations.
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PMID:Gene analyses of abnormal fibrinogens with a mutation in the gamma chain. 142 Nov 74

Molecular analysis of the human beta-galactosidase gene revealed six different mutations in 10 of 11 Japanese GM1-gangliosidosis patients. They were the only abnormalities in each allele examined in this study. A 165-nucleotide duplication (positions 1103-1267) was found in two infantile patients, producing an abnormally large mRNA; one patient was probably a homozygote, and the other was a heterozygote of this mutation. The other two infantile patients had different mutations; a 123 Gly(GGG)----Arg(AGG) mutation in one patient and a 316 Tyr(TAT)----Cys(TGT) mutation in the other. A 201 Arg(CGC)----Cys(TGC) mutation, eliminating a BspMI site, was detected in a late-infantile/juvenile patient; the restriction-site analysis of amplified genomic DNA confirmed his heterozygosity for this mutation. A 51 Ile(ATC)----Thr(ACC) mutation was found in all five adult/chronic patients examined in this study. It created a SauI site, and restriction-site analysis confirmed that four patients were homozygous mutants. The other was a compound heterozygote for this mutation and another 457 Arg(CGA)----Gln(CAA) mutation. These mutant genes expressed markedly decreased or completely deficient enzyme activities in beta-galactosidase-deficient human fibroblasts transformed by adenovirus-SV40 recombinants. We conclude that gene mutations are heterogeneous in GM1-gangliosidosis but that the 51 Ile(ATC)----Thr(ACC) mutation is common among the Japanese adult/chronic cases. Genotype-phenotype correlations in GM1-gangliosidosis are briefly discussed.
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PMID:Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases. 190

Mouse immunoglobulin heavy-chain variable region (Ig VH) genes apparently arose from the approximately 600-base-pair-long (approximately 12 tandem repeats of the 48-base-pair-long primordial building block sequence TTC-AGC-AGC-CTG-ACT-GGA-TAT-GAC-CTG-GAG-TGG-ACT-TAC-TGC-GCA-AGA) that in the original reading frame specified the amino acid sequence Phe-Ser-Ser-Leu-Thr-Gly-Tyr-Asp-Leu-Glu-Trp-Thr-Tyr-Cys-Ala-Arg. The previously identified, shorter prototype building blocks merely represented particular portions of the above primordial sequence. Even today, the direct descendant in toto of this primordial sequence specifies the last one-sixth of each VH coding sequence: the 83rd to 98th amino acid residues. Furthermore, its four truncated derivatives specify the 4th to 14th, 17th to 23rd, 29th to 37th, and 38th to 48th amino acid residues. Accordingly, all three relatively invariant--therefore, conserved--framework regions (FW-1, FW-2, and FW-3) of VHs are specified by recognizable--therefore, conserved--descendants of the primordial sequence.
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PMID:Identification of the 48-base-long primordial building block sequence of mouse immunoglobulin variable region genes. 680 49

Nature is condemned to play variations of the same theme in evolution, past commitments progressively restricting freedom of choices in evolutionary directions. While each family of genes evolved by the mechanism of gene duplication, this mechanism is extremely inefficient, the usual fate of redundant copies of the ancestral gene being degeneracy. As a result, the euchromatic DNA of higher organisms became a desert in which still-functioning genes are found scattered like oases at an average distance of 35,000 base-pairs of barren stretch between neighbors in the case of mammals. The 20-base-long sequence (AGCTG) (AGCTG) (AGCTG) (GGGTG) can be considered as one of the few ultimate ancestors of all euchromatic DNAs. Long stretches of intergenic spacers are mostly represented by degenerate subfamilies of repeats derived from the above. Certain 30- 50-base-long units of such degenerate subfamilies apparently served as the primordial building block of the ultimate ancestor of each family of genes. For example, the primordial building block of the ancestor for antigen-binding sites (variable regions) of mammalian immunoglobulin heavy chains apparently was TTC-AGC-AGC-CTG-ACT-GGA-TAT GAC-CTG-GAG-TGG-ACT-TAC-TGC-GCA-AGA, which is the original reading frame specified in the 16-amino-acid-residues-long sequence Phe-Ser-Ser-Leu-Thr-Gly-Tyr-Asp-Leu-Glu-Trp-Thr-Tyr-Cys-Ala-Arg.
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PMID:Evolution is condemned to rely upon variations of the same theme: the one ancestral sequence for genes and spacers. 682 Jan 35

To obtain direct evidence of impaired intramembrane particles (IMPs) and a deranged cytoskeletal network in situ in human red cells of band 4.2 deficiency, electron microscopic studies were performed utilizing the freeze fracture method for IMPs and the quick-freeze deep-etching method for the cytoskeletal network. Three patients with three different previously identified mutations of the band 4.2 gene, i.e., band 4.2 Komatsu (homozygous; codon 175 GAT --> TAT), band 4.2 Nippon (homozygous; codon 142 GCT --> ACT), and band 4.2 Shiga (compound heterozygous; codon 317 CGC --> TGC and codon 142 GCT --> ACT), were selected for this study. The decrease in the number of IMPs with increase in their size was most marked in band 4.2 Komatsu, which was clinically most severe with no band 4.2 protein. In this regard, in band 4.2 Nippon, which showed moderate severity in clinical hematology with a nearly missing band 4.2 protein, increased sizing was less marked. The abnormalities in IMPs were the least in band 4.2 Shiga, which demonstrated compensated hemolysis with band 4.2 protein in a trace amount. The extent of the impairment of IMPs may be reflected by the total absence or the presence of band 4.2 protein even in a trace amount and/or by the specific site(s) of the mutation of the band 4.2 gene. Derangement of the cytoskeletal network was also observed in these three patients. It was most abnormal in band 4.2 Komatsu, and less so in band 4.2 Nippon and in band 4.2 Shiga. These results clearly indicate that 1) band 4.2 plays an important role not only in its binding to band 3 but also to the skeletal network (mostly to spectrins) vertically, and 2) its deficiency produces critical abnormality in maintenance of the structural and functional integrity of the integral proteins (such as band 3), as well as the cytoskeletal network.
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PMID:Electron microscopic evidence of impaired intramembrane particles and instability of the cytoskeletal network in band 4.2 deficiency in human red cells. 863 6

Androgen insensitivity syndromes are due to defects in the androgen receptor gene. In this study, we analyzed the androgen receptor gene in four cases with complete androgen insensitivity syndrome. In patient 1, one substitutional mutation [arginine (codon CGC) to cysteine (codon TGC) at position 774] of exon F was identified. This position was located in the hormone binding domain and appeared to be one hot spot of mutations because the mutations at the same position in several unrelated cases were reported before. In patient 2, one substitutional mutation [tyrosine (codon TAT) to cysteine (codon TGT) at position 571] of exon B was identified. This position was located in the DNA binding domain. In patients 3 and 4 (siblings), one substitutional mutation [arginine (codon CGA) to glutamine (codon CAA) at position 752] of exon E was identified. Taken together, these abnormalities might be related to the pathogenesis of complete androgen insensitivity.
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PMID:Molecular analysis of the androgen receptor gene in 4 patients with complete androgen insensitivity. 954 75

Seven Bacteroides fragilis strains were cultured from samples collected from horses. From all the tested strains, as well as from the reference B. fragilis strains: enterotoxigenic NCTC 11925 and nonenterotoxigenic IPL 323 strain, DNA was isolated using Genomic DNA PREP PLUS isolation kit manufactured by A&A Biotechnology (Poland). To detect the enterotoxin (fragilysin) gene, polymerase chain reaction (PCR) was applied, using the following starters: 404 (GAG CCG AAG ACG GTG TAT GTG ATT TGT) and 407 (TGC TCA GCG CCC AGT ATA TGA CCT AGT). DNA obtained from bacterial cells was amplified in a thermocycler (Techne). The temperature profile was as follows: 1 cycle (4 min. 94 degrees C), 40 cycles (1 min. 94 degrees C, 1 min. 52 degrees C, 1 min. 74 degrees C). Amplification products were detected by electrophoresis in agarose gel (1%) with ethidium bromide added. The presence of the fragilysin gene was detected in two strains. Among the strains isolated from horses enterotoxin gene-possessing Bacteroides fragilis strains (ETBF) can be detected.
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PMID:[Enterotoxin-producing Bacteroides fragilis strains isolated from horses]. 1175 25

We report the first mutational study of thymidine kinase 1 (TK1) performed in human solid tumors. We sequenced cDNAs representing the complete coding region of TK1 in human breast (n=22) and colorectal (n=26) cancer. Codon 106 near the ATP binding site constantly differed (ATG --> GTG; Met --> Val) from the one deposited by Bradshaw and Deininger in the Genbank database (Accession number NM_003258). Silent polymorphisms at codon 11 (CCC --> CCT; Pro --> Pro) and codon 75 (GCG --> GCA; Ala --> Ala) were frequently detected in tumors as well as in normal tissues. In breast cancer the two polymorphisms were observed in 63.6% of the samples analyzed. No significant association could be found between polymorphisms and TK activity. In colorectal cancer the incidence of the two changes was 73.1% and 69.2%, respectively. Interestingly, one colon cancer with high cytosolic TK activity displayed two missense mutations located in and near the putative phosphorylation site by tyrosine kinase (s) (TAT --> CAT; Tyr --> His) and by cAMP-, cGMP-dependent protein kinase (TAC --> TGC; Tyr --> Cys), respectively; adjacent normal mucosa showed no mutation. This may open new avenues that imply TK1 activity in tumor cell proliferation.
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PMID:Mutation analysis in the coding sequence of thymidine kinase 1 in breast and colorectal cancer. 1269 56

Maple syrup urine disease (MSUD) results from mutations affecting different subunits of the mitochondrial branched-chain alpha-ketoacid dehydrogenase complex. In this study, we identified seven novel mutations in MSUD patients from Israel. These include C219W-alpha (TGC to TGG) in the E1alpha subunit; H156Y-beta (CAT to TAT), V69G-beta (GTT to GGT), IVS 9 del[-7:-4], and 1109 ins 8bp (exon 10) in the E1beta subunit; and H391R (CAC to CGC) and S133stop (TCA to TGA) affecting the E2 subunit of the branched-chain alpha-ketoacid dehydrogenase complex. Recombinant E1 proteins carrying the C219W-alpha or H156Y-beta mutation show no catalytic activity with defective subunit assembly and reduced binding affinity for cofactor thiamin diphosphate. The mutant E1 harboring the V69G-beta substitution cannot be expressed, suggesting aberrant folding caused by this mutation. These E1 mutations are ubiquitously associated with the classic phenotype in homozygous-affected patients. The H391R substitution in the E2 subunit abolishes the key catalytic residue that functions as a general base in the acyltransfer reaction, resulting in a completely inactive E2 component. However, wild-type E1 activity is enhanced by E1 binding to this full-length mutant E2 in vitro. We propose that the augmented E1 activity is responsible for robust thiamin responsiveness in homozygous patients carrying the H391R E2 mutation and that the presence of a full-length mutant E2 is diagnostic of this MSUD phenotype. The present results offer a structural and biochemical basis for these novel mutations and will facilitate DNA-based diagnosis for MSUD in the Israeli population.
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PMID:Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients: a proposed mechanism for the thiamin-responsive phenotype. 1474 28


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