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1.
Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2) 总被引:60,自引:0,他引:60
Revy P Muto T Levy Y Geissmann F Plebani A Sanal O Catalan N Forveille M Dufourcq-Labelouse R Gennery A Tezcan I Ersoy F Kayserili H Ugazio AG Brousse N Muramatsu M Notarangelo LD Kinoshita K Honjo T Fischer A Durandy A 《Cell》2000,102(5):565-575
The activation-induced cytidine deaminase (AID) gene, specifically expressed in germinal center B cells in mice, is a member of the cytidine deaminase family. We herein report mutations in the human counterpart of AID in patients with the autosomal recessive form of hyper-IgM syndrome (HIGM2). Three major abnormalities characterize AID deficiency: (1) the absence of immunoglobulin class switch recombination, (2) the lack of immunoglobulin somatic hypermutations, and (3) lymph node hyperplasia caused by the presence of giant germinal centers. The phenotype observed in HIGM2 patients (and in AID-/- mice) demonstrates the absolute requirement for AID in several crucial steps of B cell terminal differentiation necessary for efficient antibody responses. 相似文献
2.
Kuratani M Ishii R Bessho Y Fukunaga R Sengoku T Shirouzu M Sekine S Yokoyama S 《The Journal of biological chemistry》2005,280(16):16002-16008
The bacterial tRNA adenosine deaminase (TadA) generates inosine by deaminating the adenosine residue at the wobble position of tRNA(Arg-2). This modification is essential for the decoding system. In this study, we determined the crystal structure of Aquifex aeolicus TadA at a 1.8-A resolution. This is the first structure of a deaminase acting on tRNA. A. aeolicus TadA has an alpha/beta/alpha three-layered fold and forms a homodimer. The A. aeolicus TadA dimeric structure is completely different from the tetrameric structure of yeast CDD1, which deaminates mRNA and cytidine, but is similar to the dimeric structure of yeast cytosine deaminase. However, in the A. aeolicus TadA structure, the shapes of the C-terminal helix and the regions between the beta4 and beta5 strands are quite distinct from those of yeast cytosine deaminase and a large cavity is produced. This cavity contains many conserved amino acid residues that are likely to be involved in either catalysis or tRNA binding. We made a docking model of TadA with the tRNA anticodon stem loop. 相似文献
3.
4.
Alessandrini L Ciuffreda P Pavlovic R Santaniello E 《Nucleosides, nucleotides & nucleic acids》2008,27(1):31-36
The deamination rate of 2',3'-isopropylidene adenosine catalyzed by adenosine deaminase (ADA) from calf intestine and adenylate deaminase (AMPDA) from Aspergillus species has been evaluated and compared with that of the enzymatic reactions of adenosine, to elucidate the influence of the protecting group on enzyme activity. 相似文献
5.
J Spycha?a J Marsza?ek 《Comparative biochemistry and physiology. B, Comparative biochemistry》1986,83(1):169-171
Two molecular forms of AMP deaminase have been revealed by phosphocellulose column chromatography in the liver of uricotelic lizard. The calculated S0.5 value of the purified lizard liver AMP deaminase was 2.5 +/- 0.1 for the form I and 3.6 +/- 0.4 for the form II. Both forms of the enzyme were activated by ATP and ADP but the form II to a much higher extent. GTP activated only the form II and inorganic phosphate inhibited both forms. The occurrence of multiple forms of liver AMP deaminase in uricotelic species, as well as its difference from the mammalian enzyme regulation by GTP is suggested to be connected with the uricotelism in these animals. 相似文献
6.
William N. Fishbein John I. Davis K. Nagarajan John W. Winkert John W. Foellmer 《Archives of biochemistry and biophysics》1980,205(2):360-364
Rabbit antisera to human muscle adenylate deaminase efficiently precipitate this enzyme from crude homogenates of muscle from man, monkey, and horse, without affecting other enzymes and proteins in the sample. They fail to react, however, with the adenylate deaminase of purified human erythrocytes, granulocytes, lymphocytes, and platelets. The exclusive presence of an antigenic determinant in the muscle adenylate deaminase suggests that this isozyme is determined by a unique gene. Since patients with myoadenylate deaminase deficiency have normal levels of the enzyme in their erythrocytes and leukocytes, this constitutes the strongest evidence at present that the deficiency state is due to an inherited gene defect. 相似文献
7.
Perspective of plant growth promoting rhizobacteria (PGPR) containing ACC deaminase in stress agriculture 总被引:2,自引:0,他引:2
Saleem M Arshad M Hussain S Bhatti AS 《Journal of industrial microbiology & biotechnology》2007,34(10):635-648
Ethylene is a gaseous plant growth hormone produced endogenously by almost all plants. It is also produced in soil through
a variety of biotic and abiotic mechanisms, and plays a key role in inducing multifarious physiological changes in plants
at molecular level. Apart from being a plant growth regulator, ethylene has also been established as a stress hormone. Under
stress conditions like those generated by salinity, drought, waterlogging, heavy metals and pathogenicity, the endogenous
production of ethylene is accelerated substantially which adversely affects the root growth and consequently the growth of
the plant as a whole. Certain plant growth promoting rhizobacteria (PGPR) contain a vital enzyme, 1-aminocyclopropane-1-carboxylate
(ACC) deaminase, which regulates ethylene production by metabolizing ACC (an immediate precursor of ethylene biosynthesis
in higher plants) into α-ketobutyrate and ammonia. Inoculation with PGPR containing ACC deaminase activity could be helpful
in sustaining plant growth and development under stress conditions by reducing stress-induced ethylene production. Lately,
efforts have been made to introduce ACC deaminase genes into plants to regulate ethylene level in the plants for optimum growth,
particularly under stressed conditions. In this review, the primary focus is on giving account of all aspects of PGPR containing
ACC deaminase regarding alleviation of impact of both biotic and abiotic stresses onto plants and of recent trends in terms
of introduction of ACC deaminase genes into plant and microbial species. 相似文献
8.
Summary Adenosine deaminase gene frequencies in two subsamples from Northumberland (North England) show no local variation but suggest possible differences from the south of England.
Zusammenfassung Genhäufigkeiten der Adenosin-Deaminase in zwei Stichproben aus Northumberland (Nord-England) zeigen keine örtlichen Unterschiede. Dagegen sind Unterschiede zu Südengland möglich.相似文献
9.
Hitchcock DS Fedorov AA Fedorov EV Dangott LJ Almo SC Raushel FM 《Biochemistry》2011,50(25):5555-5557
Cytosine deaminase (CDA) from Escherichia coli was shown to catalyze the deamination of isoguanine (2-oxoadenine) to xanthine. Isoguanine is an oxidation product of adenine in DNA that is mutagenic to the cell. The isoguanine deaminase activity in E. coli was partially purified by ammonium sulfate fractionation, gel filtration, and anion exchange chromatography. The active protein was identified by peptide mass fingerprint analysis as cytosine deaminase. The kinetic constants for the deamination of isoguanine at pH 7.7 are as follows: k(cat) = 49 s(-1), K(m) = 72 μM, and k(cat)/K(m) = 6.7 × 10(5) M(-1) s(-1). The kinetic constants for the deamination of cytosine are as follows: k(cat) = 45 s(-1), K(m) = 302 μM, and k(cat)/K(m) = 1.5 × 10(5) M(-1) s(-1). Under these reaction conditions, isoguanine is the better substrate for cytosine deaminase. The three-dimensional structure of CDA was determined with isoguanine in the active site. 相似文献
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11.
Human mature sperm cells have a high nuclease and 5-methyldeoxycytidine monophosphate (5-mdCMP) deaminase activity. The deaminase converts the nuclease degradation product 5-mdCMP into dTMP which is further cleaved into thymine and the abasic sugar-phosphate. Both 5-methylcytidine 5' and 3' monophosphates are good substrates for the deaminase. 5-methylcytidine is not a good deaminase substrate and 5-methylcytosine (5mC) is not a substrate. A purified fraction of the deaminase free of nucleases deaminates 5mC present in intact methylated double-stranded DNA. 5-mdCMP deaminase co-purifies on SDS-PAGE with dCMP deaminase and has an apparent molecular weight of 25 kDa. The enzyme requires no divalent cations and has a Km of 1.4 x 10(-7) M for 5-mdCMP and a Vmax of 7 x 10(-11) mol/h/microg protein. The possible biological implications of the deaminase's activities in the present system are discussed. 相似文献
12.
The structural gene encoding cytidine deaminase (cdd) has been mapped in Escherichia coli K-12. It is located counterclockwise to ptsF between 46 and 47 min. The gene order in this region of the E. coli chromosome was found to be his-udk-gat-dld-cdd-ptsF. 相似文献
13.
Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells. 总被引:27,自引:0,他引:27
M Muramatsu V S Sankaranand S Anant M Sugai K Kinoshita N O Davidson T Honjo 《The Journal of biological chemistry》1999,274(26):18470-18476
We have identified a novel gene referred to as activation-induced deaminase (AID) by subtraction of cDNAs derived from switch-induced and uninduced murine B lymphoma CH12F3-2 cells, more than 80% of which switch exclusively to IgA upon stimulation. The amino acid sequence encoded by AID cDNA is homologous to that of apolipoprotein B (apoB) mRNA-editing enzyme, catalytic polypeptide 1 (APOBEC-1), a type of cytidine deaminase that constitutes a catalytic subunit for the apoB mRNA-editing complex. In vitro experiments using a glutathione S-transferase AID fusion protein revealed significant cytidine deaminase activity that is blocked by tetrahydrouridine and by zinc chelation. However, AID alone did neither demonstrate activity in C to U editing of apoB mRNA nor bind to AU-rich RNA targets. AID mRNA expression is induced in splenic B cells that were activated in vitro or by immunizations with sheep red blood cells. In situ hybridization of immunized spleen sections revealed the restricted expression of AID mRNA in developing germinal centers in which modulation of immunoglobulin gene information through somatic hypermutation and class switch recombination takes place. Taken together, these findings suggest that AID is a new member of the RNA-editing deaminase family and may play a role in genetic events in the germinal center B cell. 相似文献
14.
The functional significance of AMP deaminase and adenosine deaminase has been studied in hepatopancreas of active, aestivated and ganglionic extracts-administered snails. The activity levels of both enzymes decreased in aestivating snails. Active snails injected with ganglionic extracts of aestivated snails also showed decreased activity. Contrastingly, the hepatopancreas of aestivated snails when treated with ganglionic extracts of active snails showed increased specific activities of both enzymes. The decrease or increase in the specific activities varied with different ganglionic extracts and the significance of the same is discussed. 相似文献
15.
Adenosine triphosphate-activated adenylate deaminase from marine invertebrate animals. Properties of the enzyme from lugworm (Arenicola cristata) body-wall muscle.
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Adenylate deaminase (AMP aminohydrolase, EC 3.5.4.6) from lugworm (Arenicola cristata) body-wall muscle was partially purified by extraction in KCl solutions and chromatography on phosphocellulose. Enzyme activity was eluted from the column at two salt concentrations. Both forms show co-operative binding of AMP (Hill coefficient, h, 2.85) with s0.5 values of 20 mM and 15.6 mM. ATP and ADP act as positive effectors lowering h to 1.07 and s0.5 to 2mM. The apparent Ka (activation) for ATP was 1.5mM. GTP is an inhibitor with an apparent Ki of 0.12 mM. In vivo the ATP-activated adenylate deaminase is in the active form and may be regulated by changes in GTP concentrations. Adenylate deaminase may act as a primary ammonia-forming enzyme in ammonotelic marine invertebrates with the purine nucleotide cycle. 相似文献
16.
The beneficial effects of DNA cytidine deamination by activation-induced deaminase (AID; antibody gene diversification) and APOBEC3G (retrovirus restriction) are tempered by probable contributions to carcinogenesis. Multiple regulatory mechanisms serve to minimize this detrimental outcome. Here, we show that phosphorylation of a conserved threonine attenuates the intrinsic activity of activation-induced deaminase (Thr-27) and APOBEC3G (Thr-218). Phospho-null alanine mutants maintain intrinsic DNA deaminase activity, whereas phospho-mimetic glutamate mutants are inactive. The phospho-mimetic variants fail to mediate isotype switching in activated mouse splenic B lymphocytes or suppress HIV-1 replication in human T cells. Our data combine to suggest a model in which this critical threonine acts as a phospho-switch that fine-tunes the adaptive and innate immune responses and helps protect mammalian genomic DNA from procarcinogenic lesions. 相似文献
17.
Zahir ZA Munir A Asghar HN Shaharoona B Arshad M 《Journal of microbiology and biotechnology》2008,18(5):958-963
A series of experiments were conducted to assess the effectiveness of rhizobacteria containing 1-aminocyclopropane- 1-carboxylate (ACC) deaminase for growth promotion of peas under drought conditions. Ten rhizobacteria isolated from the rhizosphere of different crops (peas, wheat, and maize) were screened for their growth promoting ability in peas under axenic condition. Three rhizobacterial isolates, Pseudomonas fluorescens biotype G (ACC-5), P. fluorescens (ACC-14), and P. putida biotype A (Q-7), were selected for pot trial on the basis of their source, ACC deaminase activity, root colonization, and growth promoting activity under axenic conditions. Inoculated and uninoculated (control) seeds of pea cultivar 2000 were sown in pots (4 seeds/pot) at different soil moisture levels (25, 50, 75, and 100% of field capacity). Results revealed that decreasing the soil moisture levels from 100 to 25% of field capacity significantly decreased the growth of peas. However, inoculation of peas with rhizobacteria containing ACC deaminase significantly decreased the "drought stress imposed effects" on growth of peas, although with variable efficacy at different moisture levels. At the lowest soil moisture level (25% field capacity), rhizobacterial isolate Pseudomonas fluorescens biotype G (ACC-5) was found to be more promising compared with the other isolates, as it caused maximum increases in fresh weight, dry weight, root length, shoot length, number of leaves per plant, and water use efficiency on fresh and dry weight basis (45, 150, 92, 45, 140, 46, and 147%, respectively) compared with respective uninoculated controls. It is highly likely that rhizobacteria containing ACC deaminase might have decreased the drought-stress induced ethylene in inoculated plants, which resulted in better growth of plants even at low moisture levels. Therefore, inoculation with rhizobacteria containing ACC deaminase could be helpful in eliminating the inhibitory effects of drought stress on the growth of peas. 相似文献
18.
《Biochimica et Biophysica Acta (BBA) - Enzymology》1979,566(2):335-344
AMP deaminase was completely solubilized from rat skeletal muscle with 50 mM Tris-HCl buffer (pH 7.0) containing KCl at a concentration of 0.3 M or more. The purified enzyme was found to be bound to rat muscle myosin or actomyosin, but not to F-actin at KCl concentrations of less than 0.3 M. Kinetic analysis indicated that 1 mol of AMP deaminase was bound to 3 mol of myosin and that the dissociation constant (Kd) of this binding was 0.06 μM. It was also shown that AMP deaminase from muscle interacted mainly with the light meromyosin portion of the myosin molecule. This finding differs from that of Ashby and coworkers on rabbit muscle AMP deaminase, probably due to a difference in the properties of rat and rabbit muscle AMP deaminase.AMP deaminase isozymes from rat liver, kidney and cardiac muscle did not interact with rat muscle myosin. The physiological significance of this binding of AMP deaminase to myosin is discussed. 相似文献
19.
The gene encoding activation-induced cytidine deaminase (AID), a member of the cytidine deaminase family, was isolated from a murine B cell lymphoma line, CH12F3-2, induced by combined stimulation of TGF-beta, IL-4, and CD40L. We have isolated the human orthologue of mouse AID cDNA, which has an open reading frame of 198 residues containing a conserved cytidine deaminase motif. The amino acid sequence of human AID is 92% identical to that of mouse AID. RT-PCR analysis of 15 human tissues showed that AID mRNA is expressed strongly in lymph nodes and tonsils. The complete human AID gene consisting of five exons was isolated and mapped to chromosome 12p13 by fluorescence in situ hybridization. 相似文献
20.
AMP deaminase was completely solubilized from rat skeletal muscle with 50 mM Tris-HCl buffer (pH 7.0) containing KCl at a concentration of 0.3 M or more. The purified enzyme was found to be bound to rat muscle myosin or actomyosin, but not to F-actin at KCl concentrations of less than 0.3 M. Kinetic analysis indicated that 1 mol of AMP deaminase was bound to 3 mol of myosin and that the dissociation constant (Kd) of this binding was 0.06 micrometer. It was also shown that AMP deaminase from muscle interacted mainly with the light meromyosin portion of the myosin molecule. This finding differs from that of Ashby and coworkers on rabbit muscle AMP deaminase, probably due to a difference in the properties of rat and rabbit muscle AMP deaminase. AMP deaminase isozymes from rat liver, kidney and cardiac muscle did not interact with rat muscle myosin. The physiological significance of this binding of AMP deaminase to myosin is discussed. 相似文献