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31.
32.
Lee Y Hong M Kim YJ Kim JW Kim CH Lee KS Chang SY Lim JS Choe IS 《Biochemistry and molecular biology international》1999,47(1):37-46
A chromosomal DNA sequence harboring a processed AK2B pseudogene was isolated from a human genomic library. It was a variant of the AK2B gene sequence including several point mutations, deletions, and insertions. The nucleotide sequence of the ORF of the AK2B pseudogene predicted a truncated form of the AK2B mutant suggesting that the processed pseudogene is nonfunctional. A repetitive sequence, AAAAGAGAG, found in the 5' and 3' flanking regions of the pseudogene and the poly(A) tract in the 3' end junction suggest that a mRNA of AK2B may have been converted to the processed pseudogene by retrotransposition events. Previously, it was suggested that an adenylate kinase (AK) 2 related gene on chromosome 2, confirmed by Southern analysis using somatic cell hybrid cell lines, may be a processed pseudogene. It is proposed that the processed pseudogene isolated in this study may be the AK2 related nonfunctional gene localized on human chromosomes 2. 相似文献
33.
We have determined the full sequence of the ribosomal DNA intergenic spacer (IGS) of the swimming crab, Charybdis japonica, by long PCR for the first time in crustacean decapods. The IGS is 5376 bp long and contains two nonrepetitive regions separated
by one long repetitive region, which is composed mainly of four subrepeats (subrepeats I, II, III, and IV). Subrepeat I contains
nine copies of a 60-bp repeat unit, in which two similar repeat types (60 bp-a and 60 bp-b) occur alternatively. Subrepeat
II consists of nine successive repeat units with a consensus sequence length of 142 bp. Subrepeat III consists of seven copies
of another 60-bp repeat unit (60 bp-c) whose sequence is complementary to that of subrepeat I. Immediately downstream of subrepeat
III is subrepeat IV, consisting of three copies of a 391-bp repeat unit. Based on comparative analysis among the subrepeats
and repeat units, a possible evolutionary process responsible for the formation of the repetitive region is inferred, which
involves the duplication of a 60-bp subrepeat unit (60 bp-c) as a prototype.
Received: 13 April 1999 / Accepted: 2 August 1999 相似文献
34.
A 54 kDa cysteine protease purified from the crude extract of Neodiplostomum seoulense adult worms 总被引:4,自引:0,他引:4
As a preliminary study for the explanation of pathobiology of Neodiplostomum seoulense infection, a 54 kDa protease was purified from the crude extract of adult worms by sequential chromatographic methods. The crude extract was subjected to DEAE-Sepharose Fast Flow column, and protein was eluted using 25 mM Tris-HCl (pH 7.4) containing 0.05, 0.1, 0.2 and 0.4 M NaCl in stepwise elution. The 0.2 M NaCl fraction was further purified by Q-Sepharose chromatography and protein was eluted using 20 mM sodium acetate (pH 6.4) containing 0.05, 0.1, 0.2 and 0.3 M NaCl, respectively. The 0.1M NaCl fraction showed a single protein band on SDS-PAGE carried out on a 7.5-15% gradient gel. The proteolytic activities of the purified enzyme were specifically inhibited by L-trans-epoxy-succinylleucylamide (4-guanidino) butane (E-64) and iodoacetic acid. The enzyme, cysteine protease, showed the maximum proteolytic activity at pH 6.0 in 0.1 M buffer, and degraded extracellular matrix proteins such as collagen and fibronectin with different activities. It is suggested that the cysteine protease may play a role in the nutrient uptake of N. seoulense from the host intestine. 相似文献
35.
The Arabidopsis dwarf1 mutant is defective in the conversion of 24-methylenecholesterol to campesterol in brassinosteroid biosynthesis 总被引:6,自引:0,他引:6
Choe S Dilkes BP Gregory BD Ross AS Yuan H Noguchi T Fujioka S Takatsuto S Tanaka A Yoshida S Tax FE Feldmann KA 《Plant physiology》1999,119(3):897-908
Since the isolation and characterization of dwarf1-1 (dwf1-1) from a T-DNA insertion mutant population, phenotypically similar mutants, including deetiolated2 (det2), constitutive photomorphogenesis and dwarfism (cpd), brassinosteroid insensitive1 (bri1), and dwf4, have been reported to be defective in either the biosynthesis or the perception of brassinosteroids. We present further characterization of dwf1-1 and additional dwf1 alleles. Feeding tests with brassinosteroid-biosynthetic intermediates revealed that dwf1 can be rescued by 22alpha-hydroxycampesterol and downstream intermediates in the brassinosteroid pathway. Analysis of the endogenous levels of brassinosteroid intermediates showed that 24-methylenecholesterol in dwf1 accumulates to 12 times the level of the wild type, whereas the level of campesterol is greatly diminished, indicating that the defective step is in C-24 reduction. Furthermore, the deduced amino acid sequence of DWF1 shows significant similarity to a flavin adenine dinucleotide-binding domain conserved in various oxidoreductases, suggesting an enzymatic role for DWF1. In support of this, 7 of 10 dwf1 mutations directly affected the flavin adenine dinucleotide-binding domain. Our molecular characterization of dwf1 alleles, together with our biochemical data, suggest that the biosynthetic defect in dwf1 results in reduced synthesis of bioactive brassinosteroids, causing dwarfism. 相似文献
36.
Kim SU Lee KM Park SK Yoo KY Noh DY Choe KJ Ahn SH Hirvonen A Kang D 《Journal of biochemistry and molecular biology》2004,37(5):582-585
To evaluate the potential association between the GSTP1 genotype and the development of breast cancer, a hospital based case-control study was conducted on Korean women. The study population consisted of 171 histologically confirmed incident breast cancer cases and 171 age-matched controls with no present or previous history of cancer. PCR-RFLP was used for the GSTP1 genotyping and statistical evaluations were performed using an unconditional logistic regression model. Postmenopausal women with the GSTP1 Val allele were found to have a reduced risk of breast cancer (OR = 0.3, 95 % CI = 0.10-0.74). A significant interaction was observed between the GSTP1 genotype and alcohol consumption (p for interaction = 0.01); compared with never-drinking women with Ile/Ile genotype, ever-drinking women with the GSTP1 Val allele had almost a three-fold risk of breast cancer (OR = 2.9, 95 % CI = 1.05-7.85), whereas never-drinking women with Val allele had half this risk (OR = 0.5, 95 % CI = 0.27-0.93). Our findings suggest that the GSTP1 polymorphism influences individual susceptibility to breast cancer in the Korean women and this effect may be modified by alcohol consumption. 相似文献
37.
To investigate adrenomedullary radiopharmaceuticals for positron emission tomography (PET), we have developed no-carrier-added m-(omega-[18F]fluoroalkyl)benzylguanidines. m-(omega-[18F]Fluoroalkyl)benzylguanidines were prepared in two steps starting from N,N'-bis(tert-butyloxycarbonyl)-N' '-(omega-methanesulfonyloxyalkyl)benzylguanidines in 20-30% radiochemical yields (decay corrected for 100 min) and with high radiochemical purity (>97%) and shown to be stable (>90%) in an in vitro metabolic stability assay. The binding of m-(3-[18F]fluoropropyl)benzylguanidine ((18F]3) to SK-N-SH human neuroblastoma cells was temperature dependent, and binding levels at 4 degrees C were reduced to half of that at 37 degrees C, which was similar to the reduction rate observed for [123I]MIBG. Tissue distribution studies in mice showed the highest uptake in the adrenals (%ID/g = 27.2 +/- 5.0%) with relatively high uptake in the myocardium (%ID/g = 9.3 +/- 0.5%). The results suggest that this radiotracer holds promise as a useful adrenomedullary radiopharmaceutical for PET imaging. 相似文献
38.
Choe MM Sporn PH Swartz MA 《American journal of physiology. Lung cellular and molecular physiology》2003,285(2):L427-L433
Recent studies have shown that mechanical forces on airway epithelial cells can induce upregulation of genes involved in airway remodeling in diseases such as asthma. However, the relevance of these responses to airway wall remodeling is still unclear since 1). mechanotransduction is highly dependent on environment (e.g., matrix and other cell types) and 2). inflammatory mediators, which strongly affect remodeling, are also present in asthma. To assess the effects of mechanical forces on the airway wall in a relevant three-dimensional inflammatory context, we have established a tissue culture model of the human airway wall that can be induced to undergo matrix remodeling. Our model contains differentiated human bronchial epithelial cells characterized by tight junctions, cilia formation, and mucus secretion atop a collagen gel embedded with human lung fibroblasts. We found that addition of activated eosinophils and the application of 50% strain to the same system increased the epithelial thickness compared with either condition alone, suggesting that mechanical strain affects airway wall remodeling synergistically with inflammation. This integrated model more closely mimics airway wall remodeling than single-cell, conditioned media, or even two-dimensional coculture systems and is relevant for examining the importance of mechanical strain on airway wall remodeling in an inflammatory environment, which may be crucial for understanding and treating pathologies such as asthma. 相似文献
39.
Certain pathogenic trypanosomatids are highly dependent on glycolysis for ATP production, and hence their glycolytic enzymes, including glycerol-3-phosphate dehydrogenase (GPDH), are considered attractive drug targets. The ternary complex structure of Leishmania mexicana GPDH (LmGPDH) with dihydroxyacetone phosphate (DHAP) and NAD(+) was determined to 1.9A resolution as a further step towards understanding this enzyme's mode of action. When compared with the apo and binary complex structures, the ternary complex structure shows an 11 degrees hinge-bending motion of the C-terminal domain with respect to the N-terminal domain. In addition, residues in the C-terminal domain involved in catalysis or substrates binding show significant movements and a previously invisible five-residue loop region becomes well ordered and participates in NAD(+) binding. Unexpectedly, DHAP and NAD(+) appear to form a covalent bond, producing an adduct in the active site of LmGPDH. Modeling a ternary complex glycerol 3-phosphate (G3P) and NAD(+) with LmGPDH identified ten active site residues that are highly conserved among all GPDHs. Two lysine residues, Lys125 and Lys210, that are presumed to be critical in catalysis, were mutated resulting in greatly reduced catalytic activity. Comparison with other structurally related enzymes found by the program DALI suggested Lys210 as a key catalytic residue, which is located on a structurally conserved alpha-helix. From the results of site-directed mutagenesis, molecular modeling and comparison with related dehydrogenases, a catalytic mechanism of LmGPDH and a possible evolutionary scenario of this group of dehydrogenases are proposed. 相似文献
40.
Choe JY Nelson SW Arienti KL Axe FU Collins TL Jones TK Kimmich RD Newman MJ Norvell K Ripka WC Romano SJ Short KM Slee DH Fromm HJ Honzatko RB 《The Journal of biological chemistry》2003,278(51):51176-51183
A highly constrained pseudo-tetrapeptide (OC252-324) further defines a new allosteric binding site located near the center of fructose-1,6-bisphosphatase. In a crystal structure, pairs of inhibitory molecules bind to opposite faces of the enzyme tetramer. Each ligand molecule is in contact with three of four subunits of the tetramer, hydrogen bonding with the side chain of Asp187 and the backbone carbonyl of residue 71, and electrostatically interacting with the backbone carbonyl of residue 51. The ligated complex adopts a quaternary structure between the canonical R- and T-states of fructose-1,6-bisphosphatase, and yet a dynamic loop essential for catalysis (residues 52-72) is in a conformation identical to that of the T-state enzyme. Inhibition by the pseudo-tetrapeptide is cooperative (Hill coefficient of 2), synergistic with both AMP and fructose 2,6-bisphosphate, noncompetitive with respect to Mg2+, and uncompetitive with respect to fructose 1,6-bisphosphate. The ligand dramatically lowers the concentration at which substrate inhibition dominates the kinetics of fructose-1,6-bisphosphatase. Elevated substrate concentrations employed in kinetic screens may have facilitated the discovery of this uncompetitive inhibitor. Moreover, the inhibitor could mimic an unknown natural effector of fructose-1,6-bisphosphatase, as it interacts strongly with a conserved residue of undetermined functional significance. 相似文献