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)

Pregnant rats were fed six different diets from the first to the 15th, 17th or 19th day of pregnancy. Diets 1 to 5 contained the same amount of nitrogen (10% casein and unsupplemented or supplemented wheat or Bengalgram diets). Diet 6 contained 20% casein. Total placental protein, RNA, free alpha amino N contents and the activities of the enzymes arginase (EC 3.5.3.1), tyrosine amino transferase (TAT, EC 2.6.1.5) and lactate dehydrogenase (LDH, EC 1.1.1.27) were estimated. The fetal weight and placental weight, total placental protein, RNA and free alpha amino N and the activities of the enzymes increased with the gestational age, but the DNA content became constant after day 17 of gestation. The placental weight, protein, free alpha amino N and RNA contents were significantly reduced on wheat and Bengalgram diets as compared to 10% casein (control) diet. The low activities of arginase, TAT and LDH on these diets indicated impaired protein synthesis, as a result of reduction in the amino acid pool size. The fortification of wheat with lysine and Bengalgram with cystine, methionine and tryptophan showed significant improvement in the fetal weight and placental parameters. The values on the 20% casein diet were significantly higher than those observed on the 10% casein diet.
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PMID:Effect of dietary protein composition on placental protein, nucleic acid, free alpha amino N and enzymes in rats. 610 16

All mitochondrial tRNAs in the protozoan Leishmania are believed to be encoded in the nuclear genome and imported selectively into the mitochondria by an as yet unknown mechanism. Previously, we reported that two tRNAs whose genes are tightly linked were imported by mitochondria. In contrast, a tRNA encoded by a lone tRNA gene was not detectable in mitochondria. The lone tRNA gene had flanking sequences that were different from the linked genes. These studies implied a possible correlation between tRNA gene organization and gene flanking sequence, and selective tRNA import into mitochondria. Here, we report the identification of a cluster of 10 tRNA genes and show the distribution of the corresponding tRNAs in cytosolic and mitochondrial fractions. tRNA(leu)(CAG) and tRNA2(arg)(TCG) are abundant in the cytosol, but relatively scarce in mitochondria. Conversely, tRNA(ile)(TAT) and tRNA1(lys)(TTT) are abundant in mitochondria, but relatively scarce in the cytosol. tRNA(val)(TAC) and tRNA2(thr)(TGT) are barely detectable in either cellular compartment, while tRNA(gln)(TTG), tRNA1(arg)(ACG), tRNA(gly)(TCC), and tRNA(trp)(CCA) are detected in approximately equal levels in both compartments. Sequencing of the 2600 bp that comprise the tRNA gene cluster also encoding the genes for 5S RNA and URNAB RNA indicates that nucleotide composition, length, and location of genes within the cluster do not clearly correlate with import characteristics. The unexpected presence of the tRNA(trp)(CCA)-gene transcript in mitochondria is also reported. Evidence suggests that this tRNA may have unidentified base modifications at the anticodon triplet.
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PMID:A nuclear tRNA gene cluster in the protozoan Leishmania tarentolae and differential distribution of nuclear-encoded tRNAs between the cytosol and mitochondria. 793 26

South Africans of Indian origin have a high frequency of Familial Hypercholesterolemia (FH). Fibroblasts from a South African Indian FH homozygote, D, expressed about 30% of the normal number of LDL receptors. These receptors showed defective LDL binding. Sequence and haplotype analysis revealed that D had two different mutant LDL receptor alleles: FH Durban-1 is a point mutation [asp69(GAT) to tyr(TAT)] in ligand-binding repeat 2 and FH Durban-2 is a point mutation [glu119(GAG) to lys(AAG)] in ligand-binding repeat three of the LDL receptor. Single-strand conformational polymorphism analysis, which was used in the initial detection of these mutations, was also employed for subsequent population screening assays. These mutations were not detected in any of the South African Indian FH or hypercholesterolemic patients that were screened.
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PMID:Identification of two new LDL-receptor mutations causing homozygous familial hypercholesterolemia in a South African of Indian origin. 834 89

Hereditary nonpolyposis colorectal cancer (HNPCC) is frequently associated with inherited mutation in one of four DNA mismatch repair genes. Somatic mutations in the same genes are also found in a subset of sporadic colorectal cancers. A defect in DNA mismatch repair results in a RER (replication error) tumor phenotype. We screened 110 archival and 11 prospectively acquired colorectal cancers for the RER phenotype. A total of 22 cancers were RER-positive. RER-positive tumors were investigated for mutations in the DNA mismatch repair gene MLH1 using single-strand-conformation-polymorphism (SSCP) analysis. We identified four previously undescribed mutations in four different samples. Three mutations were exonic: a point mutation at codon 69 (AGG-->AAG(arg-->lys]); a single base pair deletion at codon 42/43 (GCAAAATCC-->GCAAATCC) leading to a new stop codon downstream; and a point mutation at codon 757 (TAA-->TAT [termination-->tyr] which extend the MLH1 peptide by 36 ammino acids. The fourth mutation was a 1 base pair insertion six base pairs 5' to the start of exon 14 (tttgtttt-->tttggtttt). The mutations were not seen in the patients' constitutional DNA. The somatic MLHI mutations identified appear to be causally associated with the RER phenotype.
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PMID:Four new mutations in the DNA mismatch repair gene MLH1 in colorectal cancers with microsatellite instability. Mutations in brief no. 157. Online. 1062 41

Protein transduction domains (PTDs), such as the third helix of the Drosophila Antennapedia homeobox gene (Antp) and the HIV TAT PTD, possess a characteristic positive charge on the basis of their enrichment for arginine and lysine residues. To determine whether cationic peptides are able to function as protein transduction domains, 12-mer peptide sequences from an M13 phage library were selected for synthesis on the basis of their varying cationic charge content. In addition, polylysine and polyarginine peptides were synthesized in order to assess the effect of charge contribution in protein transduction. Coupling of the biotinylated peptides to avidin-beta-galactosidase facilitated transduction in a wide variety of cell lines and primary cells, including islet beta-cells, synovial cells, polarized airway epithelial cells, dendritic cells, myoblasts, and tumor cells. Two of the peptides, PTD-4 and PTD-5, mediated transduction nearly 600-fold more efficiently than a random control peptide, but with an efficiency similar to the TAT PTD and the 12 mers of polylysine and polyarginine. Furthermore, confocal analysis of biotinylated peptide-streptavidin-Cy3 conjugates demonstrated that the internalized PTDs are found in both the nuclei and the cytoplasm of treated cells. When tested in vivo, the PTDs were able to facilitate efficient and rapid protein delivery into rabbit synovium and mouse solid tumors following intraarticular and intratumoral administration, respectively. These novel PTDs can be used to transfer therapeutic proteins and DNA for the treatment of a wide variety of diseases, including arthritis and cancer.
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PMID:Characterization of a class of cationic peptides able to facilitate efficient protein transduction in vitro and in vivo. 1102 Mar 49

Protein transduction domains (PTDs), both naturally occurring and synthetic, have been increasingly utilized to deliver biologically active agents to a variety of cell types in vitro and in vivo. We report that in addition to previously characterized arginine-rich PTDs, including TAT, lysine homopolymers were able to mediate transduction of a wide variety of cell types, as measured by flow cytometric and enzymatic assays. The efficiency of PTD-mediated transduction was influenced by the cell type tested, although polylysine homopolymers demonstrate levels of internalization that consistently exceeded those of TAT and arginine homopolymers. Transduction of arginine/lysine-rich PTDs occurred at 4 degrees C and following depletion of cellular ATP pools, albeit generally at reduced levels. Although transduction was reduced in Chinese hamster ovary mutant lines deficient in either heparan sulfate or glycosaminoglycan synthesis, uptake was restored to wild-type levels by incubating target cells with dextran sulfate. The enhancement of transduction by dextran sulfate suggests that electrostatic interactions play an important first step in the process by which PTDs and their cargo traverse the plasma membrane.
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PMID:Efficiency of protein transduction is cell type-dependent and is enhanced by dextran sulfate. 1203 49

The Escherichia coli strain WP2uvrA is widely used in general mutagenicity screening tests because of its high sensitivity to many kinds of mutagens and it serves as a supplement to the standard Salmonella typhimurium tester strains. In contrast to Salmonella His(+) revertants, E.coli Trp(+) revertants have not been characterized at the molecular level. In this study we found that in the trpE65 allele of WP2uvrA the triplet that codes for the fourth amino acid from the N-terminus of anthranilate synthetase was an ochre stop codon (TAA) instead of a glutamine codon (CAA). In spontaneous Trp(+) revertants the ochre codon had been changed to glutamine (CAA), lysine (AAA), glutamic acid (GAA), leucine (TTA), serine (TCA) or tyrosine (TAC, TAT). Since tryptophan prototrophy could also be restored by ochre suppressor mutations at the anticodon sites in the genes for tRNA(Glu) (glnU), tRNA(Lys) (lysT) and tRNA(Tyr) (tyrT, tyrU), the Trp(+) reversion system with E.coli WP2uvrA detected five types of base substitutions, A.T-->T.A, A.T-->C.G, A.T-->G.C, G.C-->A.T and G.C-->T.A. About 30-50% of Trp(+) revertants induced by N-ethyl-N'-nitro-N-nitrosoguanidine, captan and angelicin plus UVA irradiation were attributable to reversion at the trpE65 ochre locus; the others were attributable to suppressor mutations. In contrast, almost all revertants induced by N-methyl-N'-nitro-N-nitrosoguanidine, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone and furylfuramide were caused by suppressor mutations. Thus, the high mutagen sensitivity of WP2uvrA is due to several target sites consisting of A.T base pairs (trpE65, lysT) and G.C base pairs (glnU, tyrT, tyrU).
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PMID:Characterization of Trp(+) reversions in Escherichia coli strain WP2uvrA. 1211 Jun 27

Certain natural peptides and proteins of mammalian origin are able to bind and condense plasmid DNA, a prerequisite for the formation of transfection-competent complexes that facilitate nonviral gene delivery. Here we have generated recombinant derivatives of the human high-mobility group (HMG) protein HMGB2 and investigated their potential as novel protein-based transfection reagents. A truncated form of HMGB2 encompassing amino acids 1-186 of the molecule was expressed in Escherichia coli at high yield. This HMGB2186 protein purified from bacterial lysates was able to condense plasmid DNA in a concentration-dependent manner, and mediated gene delivery into different established tumor cell lines more efficiently than poly(l-lysine). By attaching, via gene fusion, additional functional domains such as the HIV-1 TAT protein transduction domain (TAT(PTD)-HMGB2186), the nuclear localization sequence of the simian virus 40 (SV40) large T-antigen (SV40(NLS)-HMGB2186), or the importin-beta-binding domain (IBB) of human importin-alpha (IBB-HMGB2186), chimeric fusion proteins were produced which displayed markedly improved transfection efficiency. Addition of chloroquine strongly enhanced gene transfer by all four HMGB2186 derivatives studied, indicating cellular uptake of protein-DNA complexes via endocytosis. The IBB-HMGB2186 molecule in the presence of the endosomolytic reagent was the most effective. Our results show that recombinant derivatives of human HMGB2 facilitate efficient nonviral gene delivery and may become useful reagents for applications in gene therapy.
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PMID:Recombinant derivatives of the human high-mobility group protein HMGB2 mediate efficient nonviral gene delivery. 1609 3

Multiple endocrine neoplasia type 1 (MEN1) is characterized by parathyroid, enteropancreatic endocrine and pituitary adenomas as well as germline mutation of the MEN1 gene. We describe 2 families with MEN1 with novel mutations in the MEN1 gene. One family was of Turkish origin, and the index patient had primary hyperparathyroidism (PHPT) plus a prolactinoma; three relatives had PHPT only. The index patient in the second family was a 46-yr-old woman of Chinese origin living in Taiwan. This patient presented with a complaint of epigastric pain and watery diarrhea over the past 3 months, and had undergone subtotal parathyroidectomy and enucleation of pancreatic islet cell tumor about 10 yr before. There was also a prolactinoma. Sequence analysis of the MEN1 gene from leukocyte genomic DNA revealed heterozygous mutations in both probands. The Turkish patient and her affected relatives all had a heterozygous A to G transition at codon 557 (AAG-->GAG) of exon 10 of MEN1 that results in a replacement of lysine by glutamic acid. The Chinese index patient and one of her siblings had a heterozygous mutation at codon 418 of exon 9 (GAC-->TAT) that results in a substitution of aspartic acid by tyrosine. In conclusion, we have identified 2 novel missense mutations in the MEN1 gene.
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PMID:Two novel mutations in the MEN1 gene in subjects with multiple endocrine neoplasia-1. 1684 Aug 30

This paper reports the disassembly of layer-by-layer (LbL) films of plasmid DNA and a reducible cationic polypeptide. To utilize a reducing microenvironment of cellular plasma membrane as a potential trigger, LbL films are assembled to contain both DNA and the TAT-based polypeptide (PTAT) with reducible disulfide bonds in the backbone. The assembly and disassembly processes are monitored by goniometry, ellipsometry, and atomic force microscopy (AFM). The structure of the PTAT films is compared with that of non-reducible poly(L-lysine) (PLL) films. Both PTAT and PLL films exhibit exponential growth but with the contact angle alternating between characteristic values. Ellipsometry and AFM show a gradual and complete disassembly of the PTAT but not the PLL films in a 24h period in the reducing environment in vitro. This study suggests a potential of using reducible LbL films for controlled DNA delivery.
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PMID:Disassembly of layer-by-layer films of plasmid DNA and reducible TAT polypeptide. 1696 57


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