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D Si

Publications and source records attributed to D Si.

9 recordsLinked to original sources
PubMed2006

On the human CYP2C9*13 variant activity reduction: a molecular dynamics simulation and docking study.

Cytochrome P450 2C9 (CYP2C9) plays a key role in the metabolism of clinical drugs. CYP2C9 is a genetically polymorphic enzyme and some of its allelic variants have less activity compared to the wild-type form. Drugs with a narrow therapeutic index may cause serious toxicity to the individuals who carry such allele. CYP2C9*13, firstly identified by some of the present authors in a Chinese poor metabolizer of lornoxicam, is characterized by mutation encoding Leu90Pro substitution. Kinetic experiments show that CYP2C9*13 has less catalytic activity in elimination of diclofenac and lornoxicam in vitro. In order to explore the structure-activity relationship of CYP2C9*13, the three-dimensional structure models of the substrate-free CYP2C9*1 and its variant CYP2C9*13 are constructed on the basis of the X-ray crystal structure of human CYP2C9*1 (PDB code 1R9O) by molecular dynamics simulations. The structure change caused by Leu90Pro replacement is revealed and used to explain the dramatic decrease of the enzymatic activity in clearance of the two CYP2C9 substrates: diclofenac and lornoxicam. The trans configuration of the bond between Pro90 and Asp89 in CYP2C9*13 is firstly identified. The backbone of residues 106-108 in CYP2C9*13 turns over and their side chains block the entrance for substrates accessing so that the entrance of *13 shrinks greatly than that in the wild-type, which is believed to be the dominant mechanism of the catalytic activity reduction. Consequent docking study which is consistent with the results of the kinetic experiments by Guo et al. identifies the most important residues for enzyme-substrate complexes.

Amino Acid Substitution↗
PubMed2005

Catalytic activities of human cytochrome P450 2C9*1, 2C9*3 and 2C9*13.

Cytochrome P450 2C9 (CYP2C9) is a geneticly polymorphic enzyme responsible for the metabolism of some clinically important drugs. CYP2C9*13 is an allele identified in a Chinese poor metabolizer of lornoxicam which has a Leu90Pro amino acid substitution. This paper reports on a study aimed at comparing the catalytic properties of CYP2C9*13 with those of the wild-type CYP2C9*1 and mutant CYP2C9*3 (Ile359Leu) in the COS-7 expression system using various substrates. CYP2C9*3 and *13 produced far lower luminescence than CYP2C9*1 in luciferin H metabolism. CYP2C9*13 exhibited an 11-fold increase in Km but no change in Vmax with tolbutamide as the substrate, a five-fold increase in Km and an 88.8% reduction in Vmax with diclofenac. These data indicate that CYP2C9*13 exhibits reduced metabolic activity toward all studied CYP2C9 substrates. The magnitude of the CYP2C9*13-associated decrease in intrinsic clearance (Vmax/Km) is greater than that associated with CYP2C9*3.

Amino Acid Substitution↗
PubMed2001

Two butylated aminooligosaccharides isolated from the culture filtrate of Streptomyces luteogriseus.

Two novel aminooligosaccharides, butytatins M03 and M13 were isolated and purified from the culture filtrate of Streptomyces luteogriseus. Analysis by liquid chromatography coupled to electrospray ionization mass spectrometry indicated their resemblance to isovalertatin, with a four-carbon acyl group. Their structures were established by NMR as aminooligosaccharide derivatives possessing a butylated side chain.

Carbon Isotopes↗
PubMed2001

Profiling of isovalertatin family aminooligosaccharides extracted from the culture of Streptomyces luteogriseus by using liquid chromatography/electrospray ionization mass spectrometry.

A rapid and novel procedure using the liquid chromatography coupled to an electrospray ionization ion trap mass spectrometry technique was applied for the profiling of isovalertatin-family aminooligosaccharides in the extract from the culture filtrate of Streptomyces luteogriseus. The aminooligosaccharides were separated on a C-8 reversed-phase column with an acetonitrile-alkaline water gradient. The desired homologues were detected using the multiple reaction monitoring mode, and the chemical structures were confirmed by analyzing the characteristic fragment ions in their collision-induced dissociation spectra. This facile procedure led to the identification of all the five known aminooligosaccharides, isovalertatins M03, M13, M23, D03, and D23, in addition to the characterization of at least 41 novel isovalertatins, the molecular weights of which ranged from 729 to 2,793. This kind of assay should be intended as a simple and convenient way for the high-throughput analysis of screening aminooligosaccharides and potentially other structural families of natural products.

Amines↗
PubMed2001

Structural revision of isovalertatins M03, M13, and M23 isolated from the culture of Streptomyces luteogriseus.

Three aminooligosaccharides, isovalertatins M03 (1), M13 (2), and M23 (3) were isolated and purified from the culture filtrate of Streptomyces luteogriseus. Their physicochemical properties, liquid chromatographic behavior, and spectroscopic data were in full accordance with the reported compounds [Xu, Q.; Wang, Q.; Lu, D. CN Patent 1100756, 1995; Chem. Abstr. 1995, 123, 110278n], but their structures were reinvestigated and revised by spectroscopic methods, including ESI multistage mass spectrometry and 2-dimensional NMR techniques.

Amines↗
PubMed2001

Biflavonoids from the aerial part of Stephania tetrandra.

Investigation of the aerial part of Stephania tetrandra led to the isolation of two biflavonoids, stephaflavone A and stephaflavone B, with a 3-6" linkage pattern, together with beta-sitosterol. Their structures were established on the basis of their spectroscopic data and their physicochemical properties.

Flavonoids↗
PubMed2000

[Trend and causes of injury deaths among children in Macheng city of Hubei province during 1969 through 1998].

OBJECTIVES: To describe time trend of mortality and proportional mortality of injury and to determine the characteristics of distribution of injury deaths in children aged 0 - 14 in Macheng city during 1969 to 1998. METHODS: Data were collected from Notification System for Deaths of Macheng City during 1969 to 1998. Injury claimed 14,510 deaths caused by injury in children in total during these years. Changes in mortality and proportional mortality for injury were fitted with log-linear and simple linear regression models to compare their difference in children with different gender and ages. RESULTS: Both injury mortality and proportional mortality in infants declined during the past 30 years, and injury mortality dropped but proportional mortality due to injury increased gradually in children aged 1 - 14 years old. From 1984 to 1998, the average injury mortality was 81.36 per 100,000 children of 0 - 14 of age, with a potential years of life lost rate was 57.92 per 1,000 children. Boys had higher injury mortality than girls. Injury mortality in infants reached 560.15 per 100,000, and mechanical suffocation was the leading cause of injury deaths in infants. Injury mortality was 95.48 per 100,000 in children aged 1 - 4 years. Injury deaths in children aged 0 - 4 accounted for 73.2 percent of total injury deaths. And, drowning was the leading cause of injury deaths in children aged 1 - 14 years. CONCLUSION: Children under five years old were the vulnerable population for injury death needed for special care and strategy and measures should be taken to control injury in children in the rural areas.

Accidents, Traffic↗
PubMed1991

[Germination temperature of seeds of medicinal plants].

According to our experiments in the last ten years, the germination behaviour of the seeds of medicinal plants may be classified into five types by different temperature requirements for germination: (1) low temperature type; (2) middle temperature type; (3) high temperature type; (4) alternating temperature type; (5) wide ranging temperature type. This classification is helpful for cultivators to determine the time of sowing.

Plants, Medicinal↗