Convergent evolution of similar function in two structurally divergent enzymes

An example of two related enzymes that catalyse similar reactions but possess different active sites is provided by comparing the structure of Escherichia coli thioredoxin reductase with glutathione reductase. Both are dimeric enzymes that catalyse the reduction of disulphides by pyridine nucleotides through an enzyme disulphide and a flavin. Human glutathione reductase contains four structural domains within each molecule: the flavin-adenine dinucleotide (FAD)- and nicotinamide-adenine dinucleotide phosphate (NADPH)-binding domains, the 'central' domain and the C-terminal domain that provides the dimer interface and part of the active site. Although both enzymes share the same catalytic mechanism and similar tertiary structures, their active sites do not resemble each other. We have determined the crystal structure of E. coli thioredoxin reductase at 2 A resolution, and show that thioredoxin reductase lacks the domain that provides the dimer interface in glutathione reductase, and forms a completely different dimeric structure. The catalytically active disulphides are located in different domains on opposite sides of the flavin ring system. This suggests that these enzymes diverged from an ancestral nucleotide-binding protein and acquired their disulphide reductase activities independently.     

窗函数法设计FIR数字滤波器的软件实现及设计原则

在研究FIR数字滤波器的设计算法基础上,按照技术指标编制了MATLAB程序.通过改变窗函数和相关参数,在比较结果的基础上,给出了具有实际意义的使用窗函数设计FIR数字滤波器的基本原则.     

人工酶与定向进化的前沿与挑战

定向进化是在实验室环境中,在分子水平上模拟进化过程,得到具有期望特征的蛋白质的方法,目前已成为蛋白质设计改造的重要方法。定向进化不仅可以用于天然蛋白质的改造,也可以通过改造现有的酶,使其具有新的催化活性,从而构建人工酶。本文重点介绍工业生物催化、纳米酶设计和光催化3个方向的前沿成果,并讨论人工酶与定向进化领域存在的挑战和问题。     

两段式差分进化算法及函数优化

针对标准差分进化算法解决不同问题时需要对控制参数进行不同的设置,提出了两段式差分进化算法.该算法利用正态分布随机数生成变异率的算子,并把进化过程分为2个阶段,不同阶段分别采用不同的交叉因子,根据不同的配置利用生成变异率来改善算法性能.同时为了加快局部寻优,利用拥有优势解的随机向量指引寻优方向.对一系列Benchmark...     

Structure-based activity prediction for an enzyme of unknown function

With many genomes sequenced, a pressing challenge in biology is predicting the function of the proteins that the genes encode. When proteins are unrelated to others of known activity, bioinformatics inference for function becomes problematic. It would thus be useful to interrogate protein structures for function directly. Here, we predict the function of an enzyme of unknown activity, Tm0936 from Thermotoga maritima, by docking high-energy intermediate forms of thousands of candidate metabolites. The docking hit list was dominated by adenine analogues, which appeared to undergo C6-deamination. Four of these, including 5-methylthioadenosine and S-adenosylhomocysteine (SAH), were tested as substrates, and three had substantial catalytic rate constants (10(5) M(-1 )s(-1)). The X-ray crystal structure of the complex between Tm0936 and the product resulting from the deamination of SAH, S-inosylhomocysteine, was determined, and it corresponded closely to the predicted structure. The deaminated products can be further metabolized by T. maritima in a previously uncharacterized SAH degradation pathway. Structure-based docking with high-energy forms of potential substrates may be a useful tool to annotate enzymes for function.     

Duplication and divergent evolution of the CHS and CHS-like genes in the chalcone synthase （CHS） superfamily

CHALCONE SYNTHASE (CHS) IS A KEY ENZYME OF FLA- VONOID BIOSYNTHESIS. IT CATALYSES THE CONDENSATION OF THREE MOLECULES OF MALONYL-COA WITH ONE MOLECULE OF 4-COUMAROYL-COA TO FORM NARINGENIN CHALCONE, THE PRECURSOR FOR A LARGE NUMBER OF FLAVONOIDS WHICH ARE WIDELY DISTRIBUTED IN THE PLANT KINGDOM AND HAVE IM- PORTANT ROLES IN FLOWER PIGMENTATION, PROTECTION AGAINST UV LIGHT A…     

服饰演化的社会环境作用

将服饰作为社会整体环境中的一定系统，着重揭示服饰系统在社会环境作用下自身形成的演化机制；并运用科学发展观的前沿研究成果，通过研究指出人类实践活动、审美活动以及社会整体环境的发展，都是服饰系统演化的客观基础，都对服饰系统演化起着基本的作用．     

Angiotensin-converting enzyme 2 is an essential regulator of heart function

Cardiovascular diseases are predicted to be the most common cause of death worldwide by 2020. Here we show that angiotensin-converting enzyme 2 (ace2) maps to a defined quantitative trait locus (QTL) on the X chromosome in three different rat models of hypertension. In all hypertensive rat strains, ACE2 messenger RNA and protein expression were markedly reduced, suggesting that ace2 is a candidate gene for this QTL. Targeted disruption of ACE2 in mice results in a severe cardiac contractility defect, increased angiotensin II levels, and upregulation of hypoxia-induced genes in the heart. Genetic ablation of ACE on an ACE2 mutant background completely rescues the cardiac phenotype. But disruption of ACER, a Drosophila ACE2 homologue, results in a severe defect of heart morphogenesis. These genetic data for ACE2 show that it is an essential regulator of heart function in vivo.     

Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast

Under laboratory conditions 80% of yeast genes seem not to be essential for viability. This raises the question of what the mechanistic basis for dispensability is, and whether it is the result of selection for buffering or an incidental side product. Here we analyse these issues using an in silico flux model of the yeast metabolic network. The model correctly predicts the knockout fitness effects in 88% of the genes studied and in vivo fluxes. Dispensable genes might be important, but under conditions not yet examined in the laboratory. Our model indicates that this is the dominant explanation for apparent dispensability, accounting for 37-68% of dispensable genes, whereas 15-28% of them are compensated by a duplicate, and only 4-17% are buffered by metabolic network flux reorganization. For over one-half of those not important under nutrient-rich conditions, we can predict conditions when they will be important. As expected, such condition-specific genes have a more restricted phylogenetic distribution. Gene duplicates catalysing the same reaction are not more common for indispensable reactions, suggesting that the reason for their retention is not to provide compensation. Instead their presence is better explained by selection for high enzymatic flux.     

一个有趣的设计性实验

将普通物理实验中,惠斯通电桥实验延伸发展成设计性实验课题：研究桥臂对电桥灵敏度的影响,让学生做理论分析和实验研究得出结论,极大地提高了学生的学习兴趣,培养了学生的科学素养和科研能力。     

现代化教育网络设计的解决方案

以因特网和多媒体等为代表的信息技术所构建的现代化教育，是知识经济时代教育发展的基石和契机，为教育的发展提供了广阔的空间，建设一个现代的教育网络，能更好地为现代化教育服务。本文就如何组建现代化教育网络提出了有关建议。     

Banach 空间中演化算子族的弱指数不稳定性

给出了Banach空间中演化算子的弱指数不稳定性的概念、演化算子的弱指数不稳定性的一些性质以及判断演化算子族弱指数不稳定的充要条件。得到了稳定性理论中的经典结论在弱指数不稳定性下的变形。     

生物系统进化的自发性准则--自适应函数

生物进化是一个非常复杂的自发过程,研究该过程对于加深对自然界的认识具有深刻意义.该文作者认为 生物进化的本质是生物为适应生存环境的变化而对自身生存状态进行的自调节; 调节过程包括生物与外界进行的质量、能量及信息的交换; 进化的结果是生物本身结构复杂性的提高.作为研究工作的第一步,该文试图从宏观热力学的角度判定生物进化过程发生的可能性.为此,提出了自适应函数φ的概念,并证明它是生物体系外界负熵的函数.利用这一概念对生物进化现象进行了讨论.当dφ < 0时,进化过程可自发进行,即其有序性增加.     

利用EvolvR系统对酶基因实现多窗口定向进化的研究

EvolvR系统是一种CRISPR介导的新型定向进化技术,本研究探索其在酶基因序列定向进化中的适用性以及突变效率,同时在此基础上扩大EvolvR的突变窗口长度.研究成功将4个能高效表达的单个sgRNA串联,并检测到靶向同一基因的3个不同靶位点.证明EvolvR具有在目标基因区域大范围制造突变的潜力,具有很高的应用价值....