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21.
22.
计算机辅助蛋白质分子理性设计在解决化学及生物学重要问题中被证实十分有效。在NOR本身三维结构未知的情况下通过计算机分子模拟,使用肌红蛋白(Mb)作为蛋白质分子模型,设计了结构功能型一氧化氮还原酶(NOR),所设计的NOR蛋白质模型——FeBMb一年后被天然NOR的晶体结构所证实。本文综述了设计FeBMb, I107E FeBMb以及FeBMb(-His)的研究过程及其设计合理性,评述了通过使用计算机分子模拟,获得Mb处于双组氨酸配位的非天然状态的原子层次结构信息,而这些信息很难通过实验方法来获得。计算机辅助蛋白质分子理性设计的广泛应用将会为生物体系提供更深刻的内涵。 相似文献
23.
Ayora-Talavera T Chappell J Lozoya-Gloria E Loyola-Vargas VM 《Applied biochemistry and biotechnology》2002,97(2):135-145
Catharanthus roseus (L.) G. Don hairy roots harboring hamster 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) (EC 1.1.1.88) cDNA without membrane-binding
domain were evaluated by quantifying the levels of sterols and some indol-alkaloids. Clone 236, with the highest hybridization
signal, had the lowest soluble and microsomal HMGR activity and produced more ajmalicine and catharanthine than the control
but had reduced campesterol concentration. Clone 19, with low hybridization signal, had high soluble HMGR activity and produced
high levels of campesterol and five to seven times more serpentine than the control but a low level of ajmalicine and no accumulation
of catharanthine. These results suggest a possible role for HMGR in indole alkaloid biosynthesis and a possible cosuppression
of both the endogenous and foreign HMGR genes in clone 236. 相似文献
24.
Recently, thioredoxin reductase as a target for treatment of tumors has attracted the attention of scientists. 1,2‐[Bis(1,2‐benzisoselenazolone‐3(2 H)‐ketone)]ethane (ethaselen, BBSKE, PCT: CN02/00412), designed and synthesized previously, is an effective thioredoxin reductase inhibitor; presently it is in phase II clinical trials, targeting gastric cancer, lung cancer and colon cancer. To seek more novel and effective anticancer drugs, we have developed many selenazole‐based compounds. Evaluation of the thioredoxin reductase inhibitory effect and investigation of the mechanism of anticancer drugs require abundant thioredoxin reductase, but since commercial thioredoxin reductase is expensive its use is often limited. Therefore, the preparation of thioredoxin reductase is necessary. Base on the above investigation, in this work we have prepared thioredoxin reductase and evaluated selenazole‐based compounds, and found that 44 compounds have high inhibitory effect on thioredoxin reductase with IC50 < 10 µ m , of which 16 compounds have IC50 values below 1 µ m . This is helpful in investigating and elucidating the mechanism of this kind of compound. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
25.
Young Hee Lee Mayavan Viji Eunhwa Lee Hyeju Jo Kyung Yoo Jaeuk Sim Sunhwan Lee Kiho Lee Heesoon Lee Jae-Kyung Jung 《Tetrahedron letters》2017,58(26):2614-2617
During the process development for multistep synthesis of Rosuvastatin calcium several impurities were obtained along with the final Rosuvastatin calcium. Out of this; synthesis of impurity A (acetone adduct) a minor impurity of Rosuvastatin calcium (3R,5S,6E)-7-[4-(4-fluorophenyl)-2-[[(2-hydroxy-2-methylpropyl)sulfonyl(methyl)amino]-6-(1-methylethyl)-pyrimidin-5-yl]-3,5-dihydroxyheptenoicacid hemicalcium salt, is described. The synthesis of impurity A has been accomplished in 6 steps; starting from formation of β-hydroxy sulfonamide as the key intermediate and followed by using convenient routes with overall yield of 13.5%. The target compound can be used as the reference substance of impurity of the Rosuvastatin calcium. 相似文献
26.
An effective method for producing methyl 4-bromo-3-hydroxybutyrate enantiomers was developed using an engineered protein. Escherichia coli transformant cells containing a mutant β-keto ester reductase (KER-L54Q) from Penicillium citrinum and a cofactor-regeneration enzyme such as glucose dehydrogenase (GDH) or Leifsonia sp. alcohol dehydrogenase (LSADH) were used to produce methyl (S)-4-bromo-3-hydroxybutyrate from methyl 4-bromo-3-oxobutyrate. On the other hand, the production of methyl (R)-4-bromo-3-hydroxybutyrate was achieved by asymmetric reduction of methyl 4-bromo-3-oxobutyrate with a mutant phenylacetaldehyde reductase (PAR-HAR1) from Rhodococcus sp. ST-10. 相似文献
27.
The conversion of 23-nor-5,20(22)E-choladienic acid-3β-ol and other intermediates of the putative norcholanic acid pathway of cardenolide biosynthesis by recombinant 3β-hydroxysteroid dehydrogenase from Digitalis lanata in dehydrogenation and reduction reactions was investigated. 23-nor-4,20(22)E-choladienic acid-3-one was found to be a substrate of recombinant progesterone 5β-reductases from D. lanata and Arabidopsis thaliana. The role of various substrates in cardenolide biosynthesis is discussed. 相似文献
28.
[MoVIO2(S2C2(CN)2)2]2− (┘1) and [MoIVO(S2C2(CN)2)2]2− (2) mimick oxidoreductase enzymatic activities of sulphite oxidase with biological electron donor, SO
3
2−
, andin vitro electron acceptor, [Fe(CN)6]3−, demonstrating proton coupled electron transfer reaction in water and inhibition of the oxidation of (2) in the presence of KCN. The sulphite exidizing system is characterized by substrate saturation kinetics indicating the biological
significance of the reactions 相似文献
29.
Koki Tsukamoto Toshio Watanabe Umpei Nagashima Yutaka Akiyama 《Journal of Molecular Structure》2005,732(1-3):87-98
A reaction mechanism of a nitric oxide reductase, cytochrome P450nor (P450nor) from Fusarium oxysporum, was clarified by using Density functional theory and Hartree–Fock calculations. In this reaction mechanism, molecular orbital (MO) analysis revealed that the NO ligand dissociates from the heme iron immediately after one-electron reduction by NADH, and MO energy analysis revealed that NADH acts as a one-electron reducer, not as a two-electron reducer, and that NADH has a pivotal role different from other one-electron reducers. The role of NADH is to act as a double one-electron donor (i.e. one-electron transfer occurring twice) and to combine with the NO− molecule by charge recombination reaction. Our quantum chemical calculations indicated that all reactions occurring in the heme pocket are too fast to become rate-limiting. Therefore, the rate-limiting steps in the proposed reaction mechanism are the process of capturing NO and NADH into the heme pocket and the process of expelling a product generated in the heme pocket. Kinetics of these processes was discussed based on large-amplitude vibration, which helps capturing and expelling processes in a widely opened heme pocket of P450nor. The reaction mechanism proposed here well explains published experimental data. 相似文献
30.
Mycobacterium tuberculosis has distinctive ability to detoxify various microbicidal superoxides and hydroperoxides via a redox catalytic cycle involving thiol reductants of peroxiredoxin (Prx) and thioredoxin (Trx) systems which has conferred on it resistance against oxidative killing and survivability within host. We have used computational approach to disrupt catalytic functions of Prx-Trx complex which can possibly render the pathogen vulnerable to oxidative killing in the host. Using protein–protein docking method, we have successfully constructed the Prx-Trx complex. Statistics of interface region revealed contact area of each monomer less than 1500 Å2 and enriched in polar amino acids indicating transient interaction between Prx and Trx. We have identified ZINC40139449 as a potent interface binding molecule through virtual screening of drug-like compounds from ZINC database. Molecular dynamics (MD) simulation studies showed differences in structural properties of Prx-Trx complex both in apo and ligand bound states with regard to root mean square deviation (RMSD), radius of gyration (Rg), root mean square fluctuations (RMSF), solvent accessible surface area (SASA) and number of hydrogen bonds (NHBs). Interestingly, we found stability of two conserved catalytic residues Cys61 and Cys174 of Prx and conserved catalytic motif, WCXXC of Trx upon binding of ZINC40139449. The time dependent displacement study reveals that the compound is quite stable in the interface binding region till 30 ns of MD simulation. The structural properties were further validated by principal component analysis (PCA). We report ZINC40139449 as promising lead which can be further evaluated by in vitro or in vivo enzyme inhibition assays. 相似文献