曲流河废弃河道的废弃类型及机理分析

分析了海拉尔河牙克石段的沉积演化特征,从沉积机制上对曲流河废弃河道进行了详细地解剖.河流截弯取直后,主流河道内不同水位与取直坝高度两者间的相互关系决定了废弃河道与主流河道的连通状态、废弃河道接收沉积物质的粒度变化.废弃河道沉积与周围点坝砂体间的岩性、物性差异使其在平面上形成连续封闭的围墙式的遮挡条带,分隔曲流带砂体形成点坝为单元的砂体组合.废弃河道的平面展布发育有2大类4小类型:串沟型、颈切型、决口改道型、串流改道型.在沉积认识的指导下,完成密井网条件下对地下废弃河道的测井、地震识别,并实例刻画了废弃河道的形态,分析了其遮挡效应.     

Structural evidence for gene duplication in the evolution of the acid proteases.

X-ray studies of acid proteases indicate a bilobal structure with a well defined active site cleft. An intramolecular twofold symmetry axis relates two topologically similar domains and the active site residues. A possible mechanism for evolution by gene duplication, divergence and gene fusion is presented.     

九寨沟Ms 7.0级地震的左旋走滑作用与动力机制

2017年8月8日四川九寨沟发生的Ms 7.0级地震是继2008年汶川Ms 8.0地震、2013年芦山Ms 7.0级地震后在青藏高原东缘发生的又一次强震。本文通过综合分析九寨沟Ms 7.0级地震及历史地震的震源机制解、余震和历史地震分布、区域应力场、活动断层等资料,来揭示九寨沟地震的发震构造与动力机制。初步研究结果表明:(1)此次地震的震中位于塔藏断裂、岷江断裂和虎牙断裂之间的交汇区,显示活动断裂的交汇区对此次地震的发生具有控制作用;(2)发震断裂为虎牙断裂,断裂走向为北西西向,倾向南西,倾角较陡,属于高倾角左旋走滑型地震;(3)震中位于虎牙断裂北段的北部地震空区,充填了1973年和1976年4次大于Mw6.0级地震空区;(4)此次地震位于2008年汶川Ms 8.0级地震的库仑应力增加区,应是汶川地震的应力传递和触发的结果;(5)此次地震位于巴颜喀拉块体的东北部顶角区,青藏高原东缘下地壳流向北东方向的挤出是驱动此次地震的动力机制。     

武汉地区丙型肝炎病毒包膜蛋白E1的生物信息学研究

使用生物信息学的方法,分析武汉地区不同基因型、亚型的丙肝病毒的包膜E1蛋白,预测其二级结构、核苷酸变异性、糖基化位点、亲水性、跨膜区、信号肽、蛋白修饰位点、B细胞抗原.结果显示各HCV的包膜E1蛋白二级结构差距不大;序列始末段有数个氨基酸残基的差距,序列上存在高变异位点,基因型2a的型内一致性最高;序列大量糖基化,有多个糖基化基化位点;序列分布着亲水性区域,基因型1b的分值很高;基因型1b、6a、3b、3a多数亚型有1个跨膜区,基因型2a多数亚型有两个跨膜区;基因型1b、6a、3b、3a无信号肽,基因型2a都有信号肽;蛋白序列上存在多个不同修饰位点和B细胞抗原,各基因型、亚型之间有明显差距,具有较大异质性.该研究为揭示病毒感染机制和研制地区性疫苗提供一定的科学依据.     

A model for interfacial activation in lipases from the structure of a fungal lipase-inhibitor complex

Lipases are hydrolytic enzymes which break down triacylglycerides into free fatty acids and glycerols. They have been classified as serine hydrolases owing to their inhibition by diethyl p-nitrophenyl phosphate. Lipase activity is greatly increased at the lipid-water interface, a phenomenon known as interfacial activation. X-ray analysis has revealed the atomic structures of two triacylglycerol lipases, unrelated in sequence: the human pancreatic lipase (hPL)4, and an enzyme isolated from the fungus Rhizomucor (formerly Mucor) miehei (RmL). In both enzymes the active centres contain structurally analogous Asp-His-Ser triads (characteristic of serine proteinases), which are buried completely beneath a short helical segment, or 'lid'. Here we present the crystal structure (at 3 A resolution) of a complex of R. miehei lipase with n-hexylphosphonate ethyl ester in which the enzyme's active site is exposed by the movement of the helical lid. This movement also increases the nonpolarity of the surface surrounding the catalytic site. We propose that the structure of the enzyme in this complex is equivalent to the activated state generated by the oil-water interface.     

Structure of the sulphiredoxin-peroxiredoxin complex reveals an essential repair embrace

Typical 2-Cys peroxiredoxins (Prxs) have an important role in regulating hydrogen peroxide-mediated cell signalling. In this process, Prxs can become inactivated through the hyperoxidation of an active site Cys residue to Cys sulphinic acid. The unique repair of this moiety by sulphiredoxin (Srx) restores peroxidase activity and terminates the signal. The hyperoxidized form of Prx exists as a stable decameric structure with each active site buried. Therefore, it is unclear how Srx can access the sulphinic acid moiety. Here we present the 2.6 A crystal structure of the human Srx-PrxI complex. This complex reveals the complete unfolding of the carboxy terminus of Prx, and its unexpected packing onto the backside of Srx away from the Srx active site. Binding studies and activity analyses of site-directed mutants at this interface show that the interaction is required for repair to occur. Moreover, rearrangements in the Prx active site lead to a juxtaposition of the Prx Gly-Gly-Leu-Gly and Srx ATP-binding motifs, providing a structural basis for the first step of the catalytic mechanism. The results also suggest that the observed interactions may represent a common mode for other proteins to bind to Prxs.     

质粒主动分配机制的研究进展

高拷贝数的质粒可以通过其较大的数量来保证它的稳定传代,但是低拷贝数的质粒只能依靠其他的方式。其中有一种被称为主动分配机制,含有分配位点。它由两个反式作用蛋白和一个顺式作用类着丝粒位点组成。其中一个蛋白是ATPase,另外一个蛋白是DNA结合蛋白,能够结合到顺式作用位点,并且与ATPase共同作用,形成分配复合物,来介导分配过程。     

Structural basis for transcription elongation by bacterial RNA polymerase

The RNA polymerase elongation complex (EC) is both highly stable and processive, rapidly extending RNA chains for thousands of nucleotides. Understanding the mechanisms of elongation and its regulation requires detailed information about the structural organization of the EC. Here we report the 2.5-A resolution structure of the Thermus thermophilus EC; the structure reveals the post-translocated intermediate with the DNA template in the active site available for pairing with the substrate. DNA strand separation occurs one position downstream of the active site, implying that only one substrate at a time can specifically bind to the EC. The upstream edge of the RNA/DNA hybrid stacks on the beta'-subunit 'lid' loop, whereas the first displaced RNA base is trapped within a protein pocket, suggesting a mechanism for RNA displacement. The RNA is threaded through the RNA exit channel, where it adopts a conformation mimicking that of a single strand within a double helix, providing insight into a mechanism for hairpin-dependent pausing and termination.     

Active site-directed protein regulation

Regulation of protein function is vital for the control of cellular processes. Proteins are often regulated by allosteric mechanisms, in which effectors bind to regulatory sites distinct from the active sites and alter protein function. Intrasteric regulation, directed at the active site and thus the counterpart of allosteric control, is now emerging as an important regulatory mechanism.     

Three-dimensional structure of CheY, the response regulator of bacterial chemotaxis

Homologies among bacterial signal transduction proteins suggest that a common mechanism mediates processes such as chemotaxis, osmoregulation, sporulation, virulence, and responses to nitrogen, phosphorous and oxygen deprivation. A common kinase-mediated phosphotransfer reaction has recently been identified in chemotaxis, nitrogen regulation, and osmoregulation. In chemotaxis, the CheA kinase passes a phosphoryl group to the cytoplasmic protein CheY, which functions as a phosphorylation-activated switch that interacts with flagellar components to regulate motility. We report here the X-ray crystal structure of the Salmonella typhimurium CheY protein. The determination of the structure was facilitated by the use of site-specific mutagenesis to engineer heavy-atom binding sites. CheY is a single-domain protein composed of a doubly wound five-stranded parallel beta-sheet. The phosphoacceptor site in CheY is probably a cluster of aspartic-acid side chains near the C-terminal edge of the beta-sheet. The pattern of sequence similarity of CheY with components of other regulatory systems can be interpreted in the light of the CheY structure and supports the view that this family of proteins have a common structural motif and active site.     

反式激活HIV-1 LTR的HHV-6基因片段B701的缺失研究

ＨＨＶ－６在体外可以激活ＨＩＶＬＴＲ引导的基因表达［１］，其基因组中一基因片段Ｂ７０１已被证明与这种激活作用有关［２］．Ｂ７０１编码１４３个氨基酸的蛋白质，可与ＨＨＶ－６基因组中其它基因片段协同作用提高对ＨＩＶＬＴＲ的激活效力．对Ｂ７０１进行缺失突变，得到突变体ＲＳＶ－Ｂ７０１－ｄ１（３′端缺失１８１个ｂｐ）、ＲＳＶ－Ｂ７０１－ｄ６（３′端缺失３５３个ｂｐ），将这两个缺失突变体分别与ＨＩＶ－Ｌｕｃ共转染受体细胞，通过ＬＵＣ活性分析发现，缺失突变体ｄ１、ｄ６不但仍具有激活能力，而且ｄ６的激活能力要远远大于ｄ１．二级结构预测初步揭示了Ｂ７０１对ＨＩＶ－ＬＴＲ的反式激活作用机制，为阐明ＨＨＶ－６基因产物与ＡＩＤＳ的病理关系提供了依据．     

Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors.

Histone deacetylases (HDACs) mediate changes in nucleosome conformation and are important in the regulation of gene expression. HDACs are involved in cell-cycle progression and differentiation, and their deregulation is associated with several cancers. HDAC inhibitors, such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), have anti-tumour effects, as they can inhibit cell growth, induce terminal differentiation and prevent the formation of tumours in mice models, and they are effective in the treatment of promyelocytic leukemia. Here we describe the structure of the histone deacetylase catalytic core, as revealed by the crystal structure of a homologue from the hyperthermophilic bacterium Aquifex aeolicus, that shares 35.2% identity with human HDAC1 over 375 residues, deacetylates histones in vitro and is inhibited by TSA and SAHA. The deacetylase, deacetylase-TSA and deacetylase-SAHA structures reveal an active site consisting of a tubular pocket, a zinc-binding site and two Asp-His charge-relay systems, and establish the mechanism of HDAC inhibition. The residues that make up the active site and contact the inhibitors are conserved across the HDAC family. These structures also suggest a mechanism for the deacetylation reaction and provide a framework for the further development of HDAC inhibitors as antitumour agents.     

Structure of a serpin-protease complex shows inhibition by deformation

The serpins have evolved to be the predominant family of serine-protease inhibitors in man. Their unique mechanism of inhibition involves a profound change in conformation, although the nature and significance of this change has been controversial. Here we report the crystallographic structure of a typical serpin-protease complex and show the mechanism of inhibition. The conformational change is initiated by reaction of the active serine of the protease with the reactive centre of the serpin. This cleaves the reactive centre, which then moves 71 A to the opposite pole of the serpin, taking the tethered protease with it. The tight linkage of the two molecules and resulting overlap of their structures does not affect the hyperstable serpin, but causes a surprising 37% loss of structure in the protease. This is induced by the plucking of the serine from its active site, together with breakage of interactions formed during zymogen activation. The disruption of the catalytic site prevents the release of the protease from the complex, and the structural disorder allows its proteolytic destruction. It is this ability of the conformational mechanism to crush as well as inhibit proteases that provides the serpins with their selective advantage.     

Challenge of new biological energy resources——Arguments on structure of active site of NiFe hydrogenase

Hydrogenases are enzymes that can reversibly split molecular hydrogen. Study on the structure of the active site and the mechanism of catalysis has drawn great attention because the results may be useful for the design of cheap biomimetic hydrogen catalysts for fuel cells, or as model for the photoproduction of H\-2. At one time the active site was generally considered to be composed of mononuclear nickel complex with ligands from the polypeptide. A breakthrough in the understanding of the structure of Hases occurred with the resolution crystal structure of D. gigas Hases in 1995. The unexpected result challenged the previously reported spectroscopic studies and caused some academic arguments. Some methods and results used for insight into Hases have to be reconsidered. Different viewpoints concerning the structure of active site of Hases in different periods and some remaining questions will be presented.     

Homing of a DNA endonuclease gene by meiotic gene conversion in Saccharomyces cerevisiae.

An unusual protein splicing reaction joins the N-terminal segment (A) and the C-terminal segment (C) of the 119K primary translation product (ABC) of the yeast VMA1 gene to yield a 69K vacuolar H(+)-ATPase subunit (AC) and an internal 50K polypeptide (B). This 50K protein is a site-specific DNA endonuclease that shares 34% identity with the homothallic switching endonuclease. The site cleaved by the VMA1-derived endonuclease exists in a VMA1 allele that lacks the derived endonuclease segment of the open reading frame. Cleavage at this site only occurs during meiosis and initiates 'homing', a genetic event that converts a VMA1 allele lacking the endonuclease coding sequence into one that contains it.     

Kunitz抑制剂家族成员抑肽酶对纤溶酶原活化的抑制作用

抑肽酶属Kunitz抑制剂家族成员，能够抑制激肽释放酶、纤溶酶及胰蛋白酶的蛋白水解活性．研究表明，抑肽酶能够抑制尿激酶型-纤溶酶原激活刹（u—PA）和组织型纤溶酶原激活剂（t—PA）对纤溶酶原的激活，但不影响u—PA和t—PA对小分子底物的酰胺水解活性．用u—PA研究了上述作用的机制，发现抑肽酶与u—PA的丝氨酸蛋白酶功能区特异性结合，而与纤溶酶原没有相互作用．抑肽酶与uPA的结合并不阻断u—PA的活性位点，因为u—PA对小分子底物的水解活性仍然保持．上述发现提示抑肽酶可能存在另一种抑制作用模式，该模式不同于以前报道的关于Kunitz抑制剂或纤溶酶原激活酶抑制剂的作用．由于人体内的Kunitz抑制剂与抑肽酶在结构上非常相似，根据研究结果，推测体内纤溶酶原的激活作用并非仅受丝氨酸蛋白酶抑制剂的控制。     

一种全局隶属度和小波能量相结合的活动轮廓模型

计算机化X射线体层照相(computeried tomography, CT),图像中的磨玻璃型肺结节,由于其具有模糊的轮廓,且肺结节区域与其邻域的亮度值相差很小等特性,一般的图像分割算法很难对其进行精准地分割。针对该问题,提出一种全局隶属度和小波能量相结合的活动轮廓模型。首先,利用全局隶属度函数调整初始活动轮廓曲线,使之与目标边界的距离更接近,且形状更相似;同时,基于全局隶属度的边界停止函数能快速收敛于目标边界,使得预测曲线更加贴合待分割目标;其次,基于小波能量的局部活动轮廓模型数据项增强了目标与背景之间的对比度,进而能更精准地分割在低对比度和亮度非均匀场景中的目标轮廓。将该模型应用于全实质及部分实质磨玻璃型肺结节的CT图像中,实验证明了本文算法的优越性。