Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Integrin alpha IIb-beta 3 binds fibrinogen via the recognition sequence Arg-Gly-Asp-Ser (RGDS). We have used the baculovirus/insect cell expression system to study the structural requirements for the formation of a functionally active fragment of alpha IIb-beta 3. A tandem baculovirus transfer vector was constructed containing the cDNA coding for the heavy chain of human alpha IIb (alpha IIbH, amino acids 1-874) and the cDNA coding for a truncated form of human beta 3 (t beta 3; amino acids 1-469). Sf9 insect cells were infected with the corresponding baculovirus, and the produced soluble recombinant proteins were purified using an RGD-like affinity column. The bound receptor fragments were specifically eluted with RGDS and existed as a heterodimeric complex (rec alpha IIbH-t beta 3) with an apparent M(r) of 160,000. In an immunocapture assay, the monoclonal antibody pl-55, which only recognizes the functionally active form of alpha IIb-beta 3, bound to the purified complex. Rec alpha IIbH-t beta 3 specifically bound 125I-fibrinogen with an affinity comparable with that of purified platelet alpha IIb-beta 3. Electron micrographs of rotary-shadowed rec alpha IIbH-t beta 3 showed that the complex had the characteristic globular head, but the two rodlike tails were 4-6 nm shorter than those found in intact alpha IIb-beta 3. Thus, the cysteine-rich repeats of beta 3 are not required for assembly, stability, and functional activity of this integrin.
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PMID:The integrin alpha IIb-beta 3, platelet glycoprotein IIb-IIIa, can form a functionally active heterodimer complex without the cysteine-rich repeats of the beta 3 subunit. 813 7

Human and ungulate embryos can catabolize amino acids for energy production, whereas rodent embryos cannot, raising the question whether studies of rodent model systems are suitable for extrapolation to the human situation. Therefore, we investigated the expression of the amino acid- and ammonia-metabolizing enzymes glutaminase, glutamate dehydrogenase, glutamine synthase, carbamoylphosphate synthase, and arginase immunohistochemically in a graded series of human embryos and fetuses. During human development the expression of these enzymes is first seen in the liver, then in the mesonephric kidney, and finally in the small intestine. Such a simultaneous expression of nitrogen-metabolizing enzymes was not seen in any other organ. The early appearance of the enzymes involved in amino acid and ammonia metabolism in the human liver, compared to, for example, the rat liver, suggests that catabolism of amino acids may provide an important supply of metabolic energy for the human embryo. The coexpression of glutaminase, glutamate dehydrogenase, and carbamoylphosphate synthase, but not of arginase, in the mesonephros and the small intestine suggests that these organs are involved in the biosynthesis of intermediates of the ornithine cycle, e.g., arginine or citrulline. From a comparison of the developmental appearance of ornithine cycle enzymes in different mammalian species we postulate that an early appearance of these enzymes is generally associated with a relatively slow prenatal growth rate and the use of amino acids as metabolic fuel.
Anat Rec 1994 Apr
PMID:Expression patterns of ammonia-metabolizing enzymes in the liver, mesonephros, and gut of human embryos and their possible implications. 819 45

We have analyzed the nucleotide sequence of complementary and genomic DNAs of the human androgen receptor (AR) gene in two siblings (patients 9006 and 9030) with receptor-positive complete androgen insensitivity (Rec(+)-CAI). Northern analysis indicated that mRNA of the AR was normal in size. However, its expression was relatively reduced in both patients. Consistent with the normal androgen-binding capacity (496 and 552 fmol/mg DNA for patients 9006 and 9030, respectively) but decreased DNA-binding ability (168 fmol/mg DNA) measured in genital skin fibroblasts, no mutation was found in both N-terminal and ligand-binding domains of the AR. However, a single base substitution (G-->A) was found in the second zinc finger of the DNA-binding domain at nucleotide 2372 of the AR cDNA in both cases. This resulted in the replacement of a highly conserved arginine residue (amino acid 614) by a histidine. When the mutated receptor plasmid was cotransfected into PC-3 cells together with the reporter chloramphenicol acetyltransferase gene, chloramphenicol acetyltransferase activity was not induced by 5 alpha-dihydrotestosterone treatment, confirming that the mutation renders the AR nonfunctional and can, therefore, be held responsible for the clinical features in these patients. These results highlight the importance of Arginine-614 in the second zinc finger of the DNA-binding domain of the AR in the protein-DNA interaction.
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PMID:A point mutation in the second zinc finger of the DNA-binding domain of the androgen receptor gene causes complete androgen insensitivity in two siblings with receptor-positive androgen resistance. 841 10

The incidence of natural scrapie in sheep is associated with polymorphisms of the PrP gene, particularly those at codons 136, 154 and 171. In many breeds, the PrP allele encoding valine at codon 136 confers an extremely high risk of scrapie, but in Suffolk sheep this allele is vanishingly rare. In this study of a single closed flock of Suffolk sheep in Scotland, scrapie occurred primarily in animals which were homozygous for glutamine at codon 171, a genotype which was significantly less frequent in healthy flockmates. However, the apparent linkage between glutamine at codon 171 and scrapie was not completely recessive because two of 64 scrapie cases were heterozygous glutamine/arginine. These results suggest that breeding for increased resistance to scrapie in Suffolks by the selection of animals according to their PrP genotype is a feasible option.
Vet Rec 1997 Jan 18
PMID:Association between natural scrapie and PrP genotype in a flock of Suffolk sheep in Scotland. 902 5

This investigation describes the migration and emergence of significant numbers of what appear to be neuron-like cells upon the surface of the median eminence of the adult rodent neurohypophyseal system of the endocrine hypothalamus following the trauma of hypophysectomy. These cells appear to migrate through the neuropil of the underlying median eminence and emerge in large numbers upon the surface of the third cerebral ventricle within 7 days following hypophysectomy (axotomy) of supraoptic (SON) and paraventricular neurites (PVN) of the adult neurohypophyseal system. Previous investigations have demonstrated regeneration of the neural stem and neural lobe in a variety of mammalian species (Adams et al., J Comp Neurol, 1969;135:121-144; Beck et al., Neuroendocrinology, 1969;5:161-182; Scott et al., Exp Neurol, 1995;131-1:23-39; Scott and Hansen, Vir Med 1997;124:249-261). It also has been demonstrated that the process of regeneration is invariably accompanied by the up-regulation of nitric oxide synthase (NOS), the enzyme that catalyzes arginine to nitric oxide (NO) and that both neurohypophyseal regeneration, as well as migration and emergence of neuron-like cells upon the surface of the adjacent third cerebral ventricle, is associated with the up-regulation of NOS and increased expression of NO. It also has been amply demonstrated that this entire process of neurohypophyseal regeneration and cell migration is completely inhibited by the introduction of the antagonist of nitric oxide, namely, nitroarginine (Scott et al., Exp Neurol, 1995;131-1:23-39; Scott and Hansen, Vir Med, 1997;124:249-261). The emergence and migratory dynamics of this novel cell line upon the floor of the rodent third cerebral ventricle are discussed with respect to the role of the ubiquitous free radical NO and the implications and potential clinical applications of neuronal migration following trauma in the human central nervous system (CNS).
Anat Rec 1999 11 01
PMID:Post-traumatic migration and emergence of a novel cell line upon the ependymal surface of the third cerebral ventricle in the adult mammalian brain. 1052 82

Heme catalases are homotetrameric enzymes with a highly conserved complex quaternary structure, and their functional role is still not well understood. Proteus mirabilis catalase (PMC), a heme enzyme belonging to the family of NADPH-binding catalases, was efficiently overexpressed in E. coli. The recombinant catalase (rec PMC) was deficient in heme with one-third heme and two-thirds protoporphyrin IX as determined by mass spectrometry and chemical methods. This ratio was influenced by the expression conditions, but the enzyme-specific activity calculated relative to the heme content remained unchanged. The crystal structure of rec PMC was solved to a resolution of 2.0 A, the highest resolution obtained to date with PMC. The overall structure was quite similar to that of wild-type PMC, and it is surprising that the absence of iron had no effect on the structure of the active site. Met 53 close to the essential His 54 was found less oxidized in rec PMC than in the wild-type enzyme. An acetate anion was modeled in an anionic pocket, away from the heme group but important for the enzymatic reaction. An alternate conformation observed for Arg 99 could play a role in the formation of the H-bond network connecting two symmetrical subunits of the tetramer.
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PMID:High-resolution structure and biochemical properties of a recombinant Proteus mirabilis catalase depleted in iron. 1248 20

Some anaerobic bacteria can efficiently eliminate one or more halide atoms from halogenated compounds such as chlorophenols and chloroethenes through reductive dehalogenation. During this process, the bacteria utilize halogenated compounds as the terminal electron acceptors in their anaerobic respiration, called dehalorespiration, to yield energy for growth. Currently the genera of Desulfitobacterium and Dehalococcoides occupy the major part of the dehalorespiring isolates. The former can acquire energy not only by dehalorespiration but also by other respirations utilizing organic compounds and metals. In sharp contrast, the latter is specialized in dehalorespiration and plays a crucial role in the detoxification of chlorinated compounds in nature. From these bacteria, various reductive dehalogenases, which catalyze the dehalogenation reaction, were purified and their corresponding genes were identified. Most reductive dehalogenases exhibit similar features such as the presences of a Tat (twin arginine translocation) signal sequence, two Fe-S clusters, and a corrinoid cofactor. Some of dehalogenase-encoding genes are found to be flanked by insertion sequences. Thus, dehalogenase genes act as a catabolic transposon, and genetic rearrangements mediated by transposable elements occur well in dehalorespirers. Moreover, the genome sequences of some dehalorespiring bacteria provide many insights into the mechanism of dehalorespiration and the evolution of a dehalogenase gene.
Chem Rec 2008
PMID:Biochemical and genetic bases of dehalorespiration. 1830 77

Comparative studies of chemosensory systems in vertebrates and invertebrates have greatly enhanced our understanding of anatomical and physiological constraints of chemical detection. Immunohistochemical comparisons of chemosensory systems are difficult to make across species due to limited cross-reactivity of mammalian-based antibodies. Immunostaining chemosensory tissues with glutaraldehyde-based antibodies generated against small metabolites in combination with hierarchical cluster analyses provide a novel approach for identifying and classifying cell types regardless of species. We used this "metabolite profiling" technique to determine whether metabolite profiles can be used to identify cell classes within and across different species including mouse, zebrafish, lobster and squid. Within a species, metabolite profiles for distinct cell classes were generally consistent. We found several metabolite-based cell classifications that mirrored function or receptor protein-based classifications. Although profiles of all six metabolites differed across species, we found that specific metabolites were associated with certain cell types. For example, elevated levels of glutathione were characteristic of nonsensory cells from vertebrates, suggesting an antioxidative role in non-neuronal cells in sensory tissues. Collectively, we found significantly different metabolite profiles for distinct cell populations in chemosensory tissue within all of the species studied. Based on their roles in other systems or cells, we discuss the roles of L-arginine, L-aspartate, L-glutamate, glycine, glutathione, and taurine within chemosensory epithelia.
Anat Rec (Hoboken) 2008 Apr
PMID:Cross-species comparison of metabolite profiles in chemosensory epithelia: an indication of metabolite roles in chemosensory cells. 1836 50

In the olfactory organ of the squid, Lolliguncula brevis there are five morphological types of olfactory receptor neurons (ORNs). Previous work to characterize odor sensitivity of squid ORNs was performed on only two of the five types in dissociated primary cell cultures. Here, we sought to establish the odorant responsiveness of all five types. We exposed live squid or intact olfactory organs to excitatory odors plus the activity marker, agmatine (AGB), an arginine derivative that enters cells through nonselective cation channels. An antibody against AGB was used to identify odorant-activated neurons. We were able to determine the ORN types of AGB-labeled cells based on their location in the epithelium, morphology and immunolabeling by a set of metabolites: arginine, aspartate, glutamate, glycine, and glutathione. Of 389 neurons identified from metabolite-labeled tissue, 3% were type 1, 32% type 2, 33% type 3, 15% type 4, and 17% type 5. Each ORN type had different odorant specificity with type 3 cells showing the highest percentages of odorant-stimulated AGB labeling. Type 1 cells were rare and none of the identified type 1 cells responded to the tested odorants, which included glutamate, alanine and AGB. Glutamate is a behaviorally attractive odorant and elicited AGB labeling in types 2 and 3. Glutamate-activated AGB labeling was significantly reduced in the presence of the adenylate cyclase inhibitor, SQ22536 (80 microM). These data suggest that the five ORN types differ in their relative abundance and odor responsiveness and that the adenylate cyclase pathway is involved in squid olfactory transduction.
Anat Rec (Hoboken) 2008 Jul
PMID:Odorant responsiveness of squid olfactory receptor neurons. 1848 2

Proprotein convertase 4 (PC4) is a member of Ca2+-dependent mammalian subtilases called Proprotein convertases (PCs) or Proprotein convertases subtilisin kexin (PCSK). PC4 plays a key role in mammalian fertilization, sperm maturation and sperm-egg fusion. Full length and C-terminal truncated rPC4 have been expressed using Leishmania tarentolae expression system. Secreted soluble enzyme was recovered in good yield from concentrate medium and purified by DEAE anion exchange and arginine-agarose column chromatographies. This is the first attempt to produce rec (recombinant) PC4 by Leishmania expression system in reasonably pure and enzymatically active form. The eluted fraction contained PC4 protein as confirmed by immunoreactivity using PC4-specific antibodies. Two protein bands at approximately 62, 53 kDa in SDS-PAGE were attributed to C-terminal truncated PC4 forms. The fraction displayed strong protease activity towards fluorogenic Boc-RVRR-MCA and various intramolecularly quenched peptides derived from PC4-substrates. It also cleaved proIGF-2 to produce active IGF-2 confirming its role in this maturation process. Moreover PC4-mediated proteolysis was efficiently blocked by a newly designed prodomain rPC4(101-116) peptide with IC(50) in low microM level. Similar but more potent PC4-inhibitory activity with K(i) in low nM range was observed with the tetrapeptide chloromethyl ketones, Dec-RVKR/K-cmk (chloromethyl ketone). The study showed that such PC4 inhibitors may find potential therapeutic and clinical applications in male fertility.
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PMID:Recombinant proprotein convertase 4 (PC4) from Leishmania tarentolae expression system: purification, biochemical study and inhibitor design. 1848 34


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