人卵清蛋白抑丝酶家族

人ov-抑丝酶家族为抑丝酶家族亚系。多数ov－抑丝酶存在细胞内,作为丝氨酸蛋白酶和半胱氨酸蛋白酶抑制剂参与蛋白质加工处理,细胞凋亡,细胞外基质重构,以及保护细胞免疫损伤等。除了蛋白酶抑制作用之外,人ov-抑丝酶家族还是有其它生物学功能。     

Serpins in plants and green algae

Control of proteolysis is important for plant growth, development, responses to stress, and defence against insects and pathogens. Members of the serpin protein family are likely to play a critical role in this control through irreversible inhibition of endogenous and exogenous target proteinases. Serpins have been found in diverse species of the plant kingdom and represent a distinct clade among serpins in multicellular organisms. Serpins are also found in green algae, but the evolutionary relationship between these serpins and those of plants remains unknown. Plant serpins are potent inhibitors of mammalian serine proteinases of the chymotrypsin family in vitro but, intriguingly, plants and green algae lack endogenous members of this proteinase family, the most common targets for animal serpins. An Arabidopsis serpin with a conserved reactive centre is now known to be capable of inhibiting an endogenous cysteine proteinase. Here, knowledge of plant serpins in terms of sequence diversity, inhibitory specificity, gene expression and function is reviewed. This was advanced through a phylogenetic analysis of amino acid sequences of expressed plant serpins, delineation of plant serpin gene structures and prediction of inhibitory specificities based on identification of reactive centres. The review is intended to encourage elucidation of plant serpin functions.     

Serpins in the Caenorhabditis elegans genome.

Data mining in genome sequences can identify distant homologues of known protein families, and is most powerful if solved structures are available to reveal the three-dimensional implications of very dissimilar sequences. Here we describe putative serpin sequences identified with very high statistical significance in the Caenorhabditis elegans genome. When mapped onto vertebrate serpins such as alpha1-antitrypsin, they suggest novel structural features. Some appear complete, some show extensive deletions, and others appear to contain only the C-terminal part of the known serpin fold, probably in partnership with N-terminal regions that have conformations unlike those of known serpins. The observation of such striking sequence similarity, in proteins that must have significantly different overall structures, substantially extends the structural characteristics of the serpin family of proteins.     

RNA Binding by Plant Serpins in vitro

Biochemistry (Moscow) - Serpins constitute a large family of protease inhibitors with regulatory functions found in all living organisms. Most plant serpins have not been functionally...     

Serpins and other covalent protease inhibitors

Serpins are irreversible covalent 'suicide' protease inhibitors. In the past two years, important advances in the structural biology of serpins have been forthcoming with the crystal structures of a covalent complex between trypsin and alpha1-antitrypsin, and of a Michaelis encounter complex between trypsin S195A and serpin 1B from Manduca sexta. These structures have helped elucidate many aspects of the mechanism of action of serpins. Also, the crystal structure of the cysteine protease caspase-8 in complex with the inhibitor p35 has revealed a new family of suicide protease inhibitors.     

Serpins: finely balanced conformational traps

Serine protease inhibitors (serpins) play very important roles in the maintenance of various physiologically important systems. As knowledge of the workings of proteins of this family grows, new understanding is gained of the mechanisms by which they inhibit target proteases, using conformational changes for which the structure of serpins is uniquely adapted. This finely balanced system is utilized to healthy benefit in the control of serpin function by modulators, arguably the most striking examples of which occur in the control of proteolytic cascades, such as the coagulation system. Serpins also play very important intracellular roles: one example is the protection of immune cells from their own cytotoxic proteases. The finely balanced serpin mechanism also means that it is prone to disastrous consequences if mutations should occur in vital positions in the serpin structure. Many examples of disease-associated mutations have been shown, which has the dual effect of highlighting how important these molecules are in the maintenance of health and the fine balance that must be maintained in order to preserve their active, inhibitory conformation.     

Serpins prevent granzyme-induced death in a species-specific manner

Expression of serine protease inhibitors (serpins) is one of the mechanisms used by tumour cells to escape immune surveillance. Previously, we have shown that expression of serpins SPI-6 and SPI-CI, respectively, renders tumour cells resistant to granzyme B (GrB)-mediated death and granzyme M (GrM)-mediated death. To obtain better insight into the interaction between serpins and their target proteases, we investigated the roles of protease inhibitor (PI)-9 and SPI-6 in the resistance to GrB-mediated and CD95-mediated death in further detail. Neither human PI-9 nor its murine orthologue SPI-6 was capable of preventing CD95-induced apoptosis in murine or human cells, indicating that these serpins do not inhibit the activation of apical caspases in this pathway. High expression of PI-9 or SPI-6 did prevent apoptosis induced by human GrB. Strikingly, only SPI-6, and not PI-9, was capable of inhibiting murine GrB, suggesting that a difference in enzymatic specificity exists between the mouse and the human granzymes. In agreement with this suggestion, murine GrB was clearly less effective in inducing apoptosis in human cells. Similar species specificity was also observed for SPI-CI and GrM when either their capacity to associate or the effectiveness of GrM-induced cytotoxicity was analysed. Our findings therefore indicate a species diversity that has a clear effect on mixed in vitro effector target settings.     

Photoregulation in prokaryotes

The spectroscopic identification of sensory rhodopsin I by Bogomolni and Spudich in 1982 provided a molecular link between the light environment and phototaxis in Halobacterium salinarum, and thus laid the foundation for the study of signal transducing photosensors in prokaryotes. In recent years, a number of new prokaryotic photosensory receptors have been discovered across a broad range of taxa, including dozens in chemotrophic species. Among these photoreceptors are new classes of rhodopsins, BLUF-domain proteins, bacteriophytochromes, cryptochromes, and LOV-family photosensors. Genetic and biochemical analyses of these receptors have demonstrated that they can regulate processes ranging from photosynthetic pigment biosynthesis to virulence.     

Glycoproteins in prokaryotes

Rather recently it has become clear that prokaryotes (Archaea and Bacteria) are able to glycosylate proteins. A literature survey revealed the different types of glycoproteins. They include mainly surface layer (S-layer) proteins, flagellins, and polysaccharide-degrading enzymes. Only in a few cases is structural information available. Many different structures have been observed that display much more variation than that observed in eukaryotes. A few studies have given evidence for the function of the prokaryotic glycoprotein glycans. Also from the biosynthetic point of view, information is rather scarce. Due to their different cell structure, prokaryotes have to use mechanisms different from those found in eukaryotes to glycosylate proteins. However, from the fragmented data available for the prokaryotic glycoproteins, similarities with the eukaryotic system can be noticed. Received: 24 February 1997 / Accepted: 13 May 1997     

Serpins Identified as Cell Growth Inhibitors in Human Plasma

We have identified a new factor, CFX, in human serum and plasma that inhibits the growth of cultured human and mouse cell lines. CFX was determined to be a negatively charged, hydrophobic glycoprotein, with a native molecular weight of 110–120 kDa and a minimal active subunit of 55 kDa. It is precipitated by 60% ammonium sulfate and is resistant to heat treatment at 100°C for 30 min. CFX was purified from human plasma to a single band on a gel which retained the cell growth inhibitory activity. Amino acid sequence analysis of the CFX band revealed sequences from four human glycoproteins, α1-antichymotrypsin, C1-esterase inhibitor, α1-antitrypsin, and α2-antiplasmin, all members of the superfamily of serpins. Of the four, C1-esterase inhibitor was shown to be the most potent cell growth inhibitor. These results suggest that serpins may play a cell growth inhibitory role in vivo, in addition to their role as protease inhibitors.     

Genome organization in prokaryotes

Most of the well-characterized prokaryotic genomes consist of double-stranded DNA organized as a single circular chromosome 0.6–10 Mb in length and one or more circular plasmid species of 2 kb-1.7 Mb. The past few years, however, have revealed some major variations in genome organization. In addition, a recent accumulation of data has shown that the location and orientation of the genes and repeated sequences (including prophages and transposons) on and among these elements is not always random. Some of the non-randomness is probably the result of unique historical events; in other cases it reflects selection for the optimization of function.     

Circadian clocks in prokaryotes

Prokaryotes have long been thought incapable of expressing circadian (daily) rhythms. Recently, however, such biological 'clocks' have been discovered in several species of cyanobacteria. These endogenous timekeepers control gene expression on a global level in cyanobacteria. Even in cyanobacterial cultures that are growing with average doubling times more rapid than one per 24 h, the circadian clock controls gene expression and cell division. We have isolated mutants of the cyanobacterial circadian pacemaker and are currently characterizing the loci responsible for their altered period phenotypes.     

Thiamin biosynthesis in prokaryotes

Twelve genes involved in thiamin biosynthesis in prokaryotes have been identified and overexpressed. Of these, six are required for the thiazole biosynthesis (thiFSGH, thiI, and dxs), one is involved in the pyrimidine biosynthesis (thiC), one is required for the linking of the thiazole and the pyrimidine (thiE), and four are kinase genes (thiD, thiM, thiL, and pdxK). The specific reactions catalyzed by ThiEF, Dxs, ThiDM, ThiL, and PdxK have been reconstituted in vitro and ThiS thiocarboxylate has been identified as the sulfur source. The X-ray structures of thiamin phosphate synthase and 5-hydroxyethyl-4-methylthiazole kinase have been completed. The genes coding for the thiamin transport system (thiBPQ) have also been identified. Remaining problems include the cloning and characterization of thiK (thiamin kinase) and the gene(s) involved in the regulation of thiamin biosynthesis. The specific reactions catalyzed by ThiC (pyrimidine formation), and ThiGH and ThiI (thiazole formation) have not yet been identified. Received: 23 August 1998 / Accepted: 16 January 1999     

Insulin-related material in prokaryotes

Abstract We have reported previously on the presence of vertebrate-type peptide hormones in Tetrahymena pyriformis and Escherichia coli . We now have examined other prokaryotes for immunologically detectable insulin-like material. The bacteria studied were E. coli, Acinetobacter calcoaceticus RAG-1, Bordetella pertussis and Halobacteria solinarium; they were grown in defined minimal salt media under varying growth conditions. All these bacteria contain insulin-related material (1–12 pg per g cell wet wt). No insulin immunoactivity was detected in the media prior to inoculation. The content of insulin-related material was not affected by the carbon source used for cell growth. These data are in good agreement with data published previously, and suggest that prokaryotes and unicellular eukaryotes are capable of producing hormone-like material; the function of these peptides, if any, is as yet unknown.     

Silent genes in prokaryotes

Abstract DNA sequence analysis provides excellent evidence for the origin of new genes, encoding new enzyme specificities or isozymes, via gene-duplication. New genes which arise in this way are likely to have arisen via silent gene intermediates. Such 'silent' genes are conceptually distinct from 'cryptic' genes which may also be silent; whereas cryptic genes are thought to be retained due to periodic selection, silent genes would be expected to have only a transient existence in the genome. Only very few of the known inactive genes are possibly (and with varying degrees of likelihood) of the 'silent' type.     

Glutathione analogs in prokaryotes

Background

Oxygen is both essential and toxic to all forms of aerobic life and the chemical versatility and reactivity of thiols play a key role in both aspects. Cysteine thiol groups have key catalytic functions in enzymes but are readily damaged by reactive oxygen species (ROS). Low-molecular-weight thiols provide protective buffers against the hazards of ROS toxicity. Glutathione is the small protective thiol in nearly all eukaryotes but in prokaryotes the situation is far more complex.

Scope of review

This review provides an introduction to the diversity of low-molecular-weight thiol protective systems in bacteria. The topics covered include the limitations of cysteine as a protector, the multiple origins and distribution of glutathione biosynthesis, mycothiol biosynthesis and function in Actinobacteria, recent discoveries involving bacillithiol found in Firmicutes, new insights on the biosynthesis and distribution of ergothioneine, and the potential protective roles played by coenzyme A and other thiols.

Major conclusions

Bacteria have evolved a diverse collection of low-molecular-weight protective thiols to deal with oxygen toxicity and environmental challenges. Our understanding of how many of these thiols are produced and utilized is still at an early stage.

General significance

Extensive diversity existed among prokaryotes prior to evolution of the cyanobacteria and the development of an oxidizing atmosphere. Bacteria that managed to adapt to life under oxygen evolved, or acquired, the ability to produce a variety of small thiols for protection against the hazards of aerobic metabolism. Many pathogenic prokaryotes depend upon novel thiol protection systems that may provide targets for new antibacterial agents. This article is part of a Special Issue entitled Cellular functions of glutathione.