Showing papers by "Hong Liu published in 2003"

Virtual Screening on Natural Products for Discovering Active Compounds and Target Information

Abstract: Natural products, containing inherently large-scale structural diversity than synthetic compounds, have been the major resources of bioactive agents and will continually play as protagonists for discovering new drugs. However, how to access this diverse chemical space efficiently and effectively is an exciting challenge for medicinal chemists and pharmacologists. While virtual screening, which has shown a great promise in drug discovery, will play an important role in digging out lead (active) compounds from natural products. This review focuses on the strategy of virtual screening based on molecular docking and, with successful examples from our laboratory, illustrates the efficiency of virtual screening in discovering active compounds from natural products. On the other hand, the sequencing of the human genome and numerous pathogen genomes has resulted in an unprecedented opportunity for discovering potential new drug targets. Chemogenomics has appeared as a new technology to initiate target discovery by using active compounds as probes to characterize proteome functions. Natural products are the ideal probes for such research. Binding affinity fingerprint is a powerful chemogenomic descriptor to characterize both small molecules and pharmacologically relevant proteins. Therefore, this review also discusses binding affinity fingerprint strategy for identifying target information from the genomic data by using natural products as the probes.

Analysis of Differential Substrate Selectivities of CYP2B6 and CYP2E1 by Site-Directed Mutagenesis and Molecular Modeling

Abstract: Human CYP2B6 and CYP2E1 were used to investigate the extent to which differential substrate selectivities between cytochrome P450 subfamilies reflect differences in active-site residues as opposed to distinct arrangement of the backbone of the enzymes. Reciprocal CYP2B6 and CYP2E1 mutants at active-site positions 103, 209, 294, 363, 367, and 477 (numbering according to CYP2B6) were characterized using the CYP2B6-selective substrate 7-ethoxy-4-trifluoromethylcoumarin, the CYP2E1-selective substrate p -nitrophenol, and the common substrates 7-ethoxycoumarin, 7-butoxycoumarin, and arachidonic acid. This report is the first to study the active site of CYP2E1 by systematic site-directed mutagenesis. One of the most intriguing findings was that substitution of CYP2E1 Phe-477 with valine from CYP2B6 resulted in significant 7-ethoxy-4-trifluoromethylcoumarin deethylation. Use of three-dimensional models of CYP2B6 and CYP2E1 based on the crystal structure of CYP2C5 suggested that deethylation of 7-ethoxy-4-trifluoromethylcoumarin by CYP2E1 is impeded by van der Waals overlaps with the side chain of Phe-477. Interestingly, none of the CYP2B6 mutants acquired enhanced ability to hydroxylate p -nitrophenol. Substitution of residue 363 in CYP2E1 and CYP2B6 resulted in significant alterations of the metabolite profile for the side chain hydroxylation of 7-butoxycoumarin. Probing of CYP2E1 mutants with arachidonic acid indicated that residues Leu-209 and Phe-477 are critical for substrate orientation in the active site. Overall, the study revealed that differences in the side chains of active-site residues are partially responsible for differential substrate selectivities across cytochrome P450 subfamilies. However, the relative importance of active-site residues appears to be dependent on the structural similarity of the compound to other substrates of the enzyme.

Homotropic versus heterotopic cooperativity of cytochrome P450eryF: a substrate oxidation and spectral titration study.

Abstract: P450eryF is the only bacterial P450 to show cooperativity of substrate binding and oxidation. However, the studies reported so far have provided evidence only for homotropic cooperativity of P450eryF but not for heterotropic cooperativity. Therefore, oxidation of 7-benzyloxyquinoline (7-BQ) and 1-pyrenebutanol (1-PB) by P450eryF A245T and spectral binding of 9-aminophenanthrene (9-AP) to wild-type P450eryF were investigated in the presence of various effectors. The addition of steroids and flavones caused no stimulation but rather moderate inhibition of 7-BQ or 1-PB oxidation by P450eryF A245T. However, the binding affinity of 9-AP was significantly increased in the presence of androstenedione or α-naphthoflavone (ANF). A comparative study with CYP3A4 revealed a similar increase in the binding affinity of 9-AP for the enzyme at low ANF concentrations but some competition at higher ANF concentrations. These studies, to our knowledge, provide the first report of heterotropic cooperativity in P450eryF as well as spectroscopic evidence for simultaneous presence of two ligand molecules in the CYP3A4 active site.

Pseudomonas offensire smell ZWL 73 and its making method and application

Abstract: A malodorus pseudomonads ZWL73 used for degradating 1-chloro-4-nitrobenzene is prepared through preparing inorganic salt-type culture medium, enriching its bacterial strains, and separating.

Preparation method of spherical agglomeration less yttrium aluminium garnet nano micropowder

Abstract: A process for preparing the non-coagulation spherical nano-class microparticles of yttrium aluminium garnet (YAG) includes such steps as providing the cheap raw materials containing yttrium and aluminium preparing hydrate of aluminium and yttrium, washing, adding disperser and crystal shape controlling agent, dispersing in the aqueous solution of organic solvent, and heating to 150-350 deg.C in sealed container. Its advantages are simple process, low cost and uniform granularity.

A Dendrite with "Sierpinski Gasket" Fractal Morphology in Matt Glaze of LiAlSiO4-SiO2 System

Abstract: In this paper, we introduce a dendritic crystal, formed in matt glaze of LiAlSiO4-SiO2, having "Sierpinski gasket" fractal morphology. The crystal structure of this "Sierpinski gasket" dendrite is β-quartz. β-quartz can grow two kinds of fractal patterns: snow-shaped dendrite and "Sierpinski gasket" dendrite, depending on different supercooling conditions. These two kinds of fractals can develop together in one dendritic crystal. The evolution of the boundary morphologies between these two kinds of fractal dendrites can be described by another fractal — Koch curve. The "Sierpinski gasket" dendrite is a rather new fractal growth pattern which can introduce new opportunities to fractal growth research of nonlinear sciences.