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1.
Structural and functional characterization of second-coordination sphere mutants of soybean lipoxygenase-1. 总被引:2,自引:0,他引:2
Lipoxygenases are an important class of non-heme iron enzymes that catalyze the hydroperoxidation of unsaturated fatty acids. The details of the enzymatic mechanism of lipoxygenases are still not well understood. This study utilizes a combination of kinetic and structural probes to relate the lipoxygenase mechanism of action with structural modifications of the iron's second coordination sphere. The second coordination sphere consists of Gln(495) and Gln(697), which form a hydrogen bond network between the substrate cavity and the first coordination sphere (Asn(694)). In this investigation, we compared the kinetic and structural properties of four mutants (Q495E, Q495A, Q697N, and Q697E) with those of wild-type soybean lipoxygenase-1 and determined that changes in the second coordination sphere affected the enzymatic activity by hydrogen bond rearrangement and substrate positioning through interaction with Gln(495). The nature of the C-H bond cleavage event remained unchanged, which demonstrates that the mutations have not affected the mechanism of hydrogen atom tunneling. The unusual and dramatic inverse solvent isotope effect (SIE) observed for the Q697E mutant indicated that an Fe(III)-OH(-) is the active site base. A new transition state model for hydrogen atom abstraction is proposed. 相似文献
2.
MOTIVATION: A realistic approach to sequencing by hybridization must deal with realistic sequencing errors. The results of such a method can surely be applied to similar sequencing tasks. RESULTS: We provide the first algorithms for interactive sequencing by hybridization which are robust in the presence of hybridization errors. Under a strong error model allowing both positive and negative hybridization errors without repeated queries, we demonstrate accurate and efficient reconstruction with error rates up to 7%. Under the weaker traditional error model of Shamir and Tsur (Proceedings of the Fifth International Conference on Computational Molecular Biology (RECOMB-01), pp 269-277, 2000), we obtain accurate reconstructions with up to 20% false negative hybridization errors. Finally, we establish theoretical bounds on the performance of the sequential probing algorithm of Skiena and Sundaram (J. Comput. Biol., 2, 333-353, 1995) under the strong error model. AVAILABILTY: Freely available upon request. CONTACT: skiena@cs.sunysb.edu. 相似文献
3.
Previous studies have shown that the development anomaly encountered in meristem culture, known as vitreous plants, is due to deficient lignin synthesis. This anomaly can be cured by addition of phloridzin to the culture medium. This study examines the activities of some enzymes involved in the synthesis of lignins and of flavonoids in normal and in vitreous plants of two apple cultivars. The results showed that all enzymes were consistently less active in the vitreous plants. This agrees with previous studies made on the hydroxycinnamate: CoA ligase activity in Prunus avium (L.) meristem-derived plants. The study on the substrate specificity of the enzyme demonstrates that while its activity is lower in the vitreous plant, its conformation is identical with that of the normal plant; the substrate that is specific to enzyme extracts of both sources is para-coumaric acid. 相似文献
4.
C Lefevre H H Phan A Anteunis G Rosselin 《The journal of histochemistry and cytochemistry》1990,38(9):1257-1266
Transferrin (Tf) and vasoactive intestinal peptide (VIP) were labeled with horseradish peroxidase (HRP) and 125I, respectively. To determine whether two simultaneously incubated ligands are conveyed by the same population of endosomal vesicles in human colon carcinoma cells (HT-29), we used an analysis system derived from the cross-fire method for quantitation of autoradiographic data. This system permitted the collection of data and the statistical calculations required by the double labeling of the cells. HRP-labeled Tf organelles were chosen as reference structures of the endosomal apparatus and taken as the conventional source of the radiolabeling. Our data established from the co-localization hypothesis strongly suggest that after a 30-sec (T 1/2) and a 10-min (T10) internalization at 37 degrees C, VIP and Tf share in major part the same endocytic pathway and even the recycling route to the cell surface. At T10, most of the radiolabeling was located inside the tubulovesicular network, and we also detected slight radiolabeling inside the vesicles recycling Tf. The number of double-labeled endosomes involved in ligand traffic were advantageously observed with our computer-assisted analysis system. 相似文献
5.
The effect of diabetes mellitus on serum cholesterol and aortic microsomal prostanoid synthesis was studied in cholesterol fed male Lewis rats. Normal, diabetic and diabetic rats treated with pancreatic islets were divided into three diet subgroups, control diet, control +2% cholesterol for 8 weeks and control +2% cholesterol diet for 16 weeks. Serum glucose levels were elevated three-fold in the diabetic group compared to normal. Treatment with islets restored serum glucose to normal levels in diabetic rats. The 2% cholesterol diet did not significantly alter serum glucose levels in any of the groups. Body weights in the diabetic group were significantly lower than normal or diabetic rats treated with islets. Feeding 2% cholesterol for 16 weeks significantly increased weight in normal and islet treated diabetic rats but not in the diabetic group. Aortic microsomal prostanoid synthesis was similar in all experimental groups with 6-keto-PGF1 alpha (PGI2 metabolite) being the major product synthesized in all groups. Aortic microsomal prostanoid levels were not altered by the 2% cholesterol diet. Serum cholesterol levels increased 14-fold in the diabetic group which returned to the normal level in the diabetic animals treated with islets. These data show that diabetes does not alter aortic microsomal prostanoid levels in the rat. However, diabetes significantly increased serum cholesterol levels which were reversed by islet transplantation. 相似文献
6.
Vicente Gomes Phan Van Ngan Claude de Broyer Maria José deA. C. Rocha Passos 《Hydrobiologia》1993,262(2):109-113
Mitotic and meiotic chromosomes of the Antarctic lysianassoid amphipod Waldeckia obesa are described. The modal chromosome number is n = 25 and 2n = 50. The potential applications of cytogenetical studies in this group are discussed. 相似文献
7.
Bui Hai Ninh Duong Thi Dung Bui Huu Tai Pham Hai Yen Nguyen Xuan Nhiem Truong Thi Thu Hien Do Thi Trang Nguyen Van Tuyen Le Tuan Anh Nguyen Thi Hoai Phan Van Kiem 《化学与生物多样性》2023,20(3):e202201048
A new isopropyl chromone ( 1 ) and a new flavanone glucoside ( 2 ) together with eleven known compounds ( 3–13 ) were isolated from the leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry. Their structures were elucidated as 5,7-dihydroxy-2-isopropyl-6,8-dimethyl-4H-chromen-4-one ( 1 ), 5,7-dihydroxyflavanone 7-O-β-D-(6′′-O-galloylglucopyranoside) ( 2 ), strobopinin ( 3 ), demethoxymatteucinol ( 4 ), pinocembrin-7-O-β-D-glucopyranoside ( 5 ), (2S)-hydroxynaringenin-7-O-β-D-glucopyranoside ( 6 ), afzelin ( 7 ), quercetin ( 8 ), kaplanin ( 9 ), endoperoxide G3 ( 10 ), grasshopper ( 11 ), vomifoliol ( 12 ), litseagermacrane ( 13 ) by the analysis of HR-ESI-MS, NMR, and CD spectral data. Compounds 1 , 2 , 5 , 6 and 10 inhibited NO production on LPS-activated RAW264.7 cells with IC50 values of 12.28±1.15, 8.52±1.62, 7.68±0.87, 9.67±0.57, and 6.69±0.34 μM, respectively, while the IC50 values of the other compounds ranging from 33.38±0.78 to 86.51±2.98 μM, compared to that of the positive control, NG-monomethyl-L-arginine acetate (L-NMMA) with an IC50 value of 32.50±1.00 μM. 相似文献
8.
Summary Using a combinatorial peptide library method, we identified YIYGSFK as an efficient and specific peptide substrate for pp60c-src protein tyrosine kinase (PTK) [Lam et al., Int. J. Pept. Protein Res., 45 (1995) 587]. Employing YIYGSFK as a template, we synthesized and evaluated a series of pseudosubstrate-based inhibitors for pp60c-src. We found that the efficiency of a given inhibitor was highly dependent on the specific tyrosine analog used at the phosphorylation site of the substrate. One of these pseudosubstrate inhibitors, YI(2-Nal)GSFK, selectively inhibited the kinase activity of pp60c-src, with a Ki of 24 M. This peptide inhibitor exhibited selectivity for pp60c-src as compared to other PTKs tested, such as c-Abl and Bcr-Abl. Our results suggest that selective inhibitors for a specific PTK can be developed when the structure of a specific and efficient small peptide substrate for this PTK can be used as a template for structure modification.Abbreviations 1-Nal
l-1-naphthylalanine
- 2-Nal
l-2-naphthylalanine
- BOP
benzotriazolyl-N-oxy-tris(dimethylamino)-phosphonium hexafluorophosphate
- BSA
bovine serum albumin
- cAPK
cyclic AMP-dependent protein kinase
- DIEA
diisopropylethylamine
- EGFR
epidermal growth factor receptor
- Fmoc
fluorenylmethoxycarbonyl
- HOBt
1-hydroxybenzotriazole
- MES
2-[N-morpholino]ethanesulfonic acid
- PBS
phosphate-buffered salts
- pCl
l-p-chlorophenylalanine
- pF
l-p-fluorophenylalanine
- PTK
protein tyrosine kinase
- TLC
thin-layer chromatography 相似文献
9.
Prostaglandins of the E-series (PGEs) and PGI2 will inhibit formylmethionylleucylphenylalanine-(f-Met-Leu-Phe) induced lysosomal enzyme release and superoxide-anion (O2-) production by neutrophils. The inhibitory effects of PGEs and PGI2 on neutrophil functional responses have been correlated with their ability to increase intracellular cAMP. In this study we have examined the effects of PGEs and PGI2 on f-Met-Leu-Phe- and phorbol-myristate-acetate-induced rat neutrophil membrane potential changes using an optical probe of membrane potential 3,3-dipropylthiodicarbocyanine iodide. 15-(S)-15-methyl-PGE1 (15-methyl-PGE1), a stable analogue of PGE1 and PGI2 inhibited f-Met-Leu-Phe-induced transmembrane potential changes in a dose-dependent manner. This inhibition was correlated with the ability of these agents to increase intracellular cAMP levels and inhibit O2- production and degranulation. In contrast, 15-methyl-PGE1 and PGI2, did not inhibit phorbol-myristate-acetate-induced transmembrane potential changes and O2- production. These results suggest independent mechanisms of activation of neutrophils by phorbol myristate acetate and f-Met-Leu-Phe, and they also suggest that the inhibitory effects of prostaglandins and cAMP on f-Met-Leu-Phe-stimulated cells is at a step or steps prior to activation of those processes involved in effecting changes in transmembrane potential, which are common to both stimuli. 相似文献
10.
[3H]spiroperidol binding has been measured in lymphocytes from patients with Parkinson's disease and age matched healthy volunteers. A dramatic decrease (73%) in the number of binding sites (Bmax) without any variation of the affinity (KD) has been observed in Parkinsonian patients. This decrease in Bmax is linearly correlated with the degree of disability of the Parkinsonian patients (r = 0.891, p <0.001). This decrease appeared to be relatively selective since no variation was observed with patients suffering of other neurological disorders (vascular hemiplegia, Alzeihmer's disease, olivopontocerebellar degeneration, Huntington's chorea). 相似文献