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1.
The RNA-splicing endonuclease is an evolutionarily conserved enzyme responsible for the excision of introns from nuclear transfer
RNA (tRNA) and all archaeal RNAs. Since its first identification from yeast in the late 1970s, significant progress has been
made toward understanding the biochemical mechanisms of this enzyme. Four families of the splicing endonucleases possessing
the same active sites and overall architecture but with different subunit compositions have been identified. Two related consensus
structures of the precursor RNA splice sites and the critical elements required for intron excision have been established.
More recently, a glimpse was obtained of the structural mechanism by which the endonuclease recognizes the consensus RNA structures
and cleaves at the splice sites. This review summarizes these findings and discusses their implications in the evolution of
intron removal processes.
Received 24 August 2007; received after revision 24 November 2007; accepted 27 November 2007 相似文献
2.
Pepsinogens, progastricsins, and prochymosins: structure, function, evolution, and development 总被引:12,自引:0,他引:12
Kageyama T 《Cellular and molecular life sciences : CMLS》2002,59(2):288-306
Five types of zymogens of pepsins, gastric digestive proteinases, are known: pepsinogens A, B, and F, progastricsin, and
prochymosin. The amino acid and/or nucleotide sequences of more than 50 pepsinogens other than pepsinogen B have been determined
to date. Phylogenetic analyses based on these sequences indicate that progastricsin diverged first followed by prochymosin,
and that pepsinogens A and F are most closely related. Tertiary structures, clarified by X-ray crystallography, are commonly
bilobal with a large active-site cleft between the lobes. Two aspartates in the center of the cleft, Asp32 and Asp215, function
as catalytic residues, and thus pepsinogens are classified as aspartic proteinases. Conversion of pepsinogens to pepsins proceeds
autocatalytically at acidic pH by two different pathways, a one-step pathway to release the intact activation segment directly,
and a stepwise pathway through a pseudopepsin(s). The active-site cleft is large enough to accommodate at least seven residues
of a substrate, thus forming S4 through S3′ subsites. Hydrophobic and aromatic amino acids are preferred at the P1 and P1′ positions. Interactions at additional subsites are important in some cases, for example with cleavage of κ-casein by chymosin. Two potent naturally occurring inhibitors are known: pepstatin, a pentapeptide from Streptomyces, and a unique proteinous inhibitor from Ascaris. Pepsinogen genes comprise nine exons and may be multiple, especially for pepsinogen A. The latter and progastricsin predominate
in adult animals, while pepsinogen F and prochymosin are the main forms in the fetus/infant. The switching of gene expression
from fetal/infant to adult-type pepsinogens during postnatal development is noteworthy, being regulated by several factors,
including steroid hormones.
Received 25 May 2001; received after revision 27 August 2001; accepted 30 August 2001 相似文献
3.
Thomas M. A. Shafee Fung T. Lay Thanh Kha Phan Marilyn A. Anderson Mark D. Hulett 《Cellular and molecular life sciences : CMLS》2017,74(4):663-682
Defensins are a well-characterised group of small, disulphide-rich, cationic peptides that are produced by essentially all eukaryotes and are highly diverse in their sequences and structures. Most display broad range antimicrobial activity at low micromolar concentrations, whereas others have other diverse roles, including cell signalling (e.g. immune cell recruitment, self/non-self-recognition), ion channel perturbation, toxic functions, and enzyme inhibition. The defensins consist of two superfamilies, each derived from an independent evolutionary origin, which have subsequently undergone extensive divergent evolution in their sequence, structure and function. Referred to as the cis- and trans-defensin superfamilies, they are classified based on their secondary structure orientation, cysteine motifs and disulphide bond connectivities, tertiary structure similarities and precursor gene sequence. The utility of displaying loops on a stable, compact, disulphide-rich core has been exploited by evolution on multiple occasions. The defensin superfamilies represent a case where the ensuing convergent evolution of sequence, structure and function has been particularly extreme. Here, we discuss the extent, causes and significance of these convergent features, drawing examples from across the eukaryotes. 相似文献
4.
A-, F- and V-adenosine 5'-triphosphatases (ATPases) consist of a mosaic of globular structural units which serve as functional units. These ion-translocating ATPases are thought to use a common mechanism to couple energy of ATP hydrolysis to ion transport and thus create an electrochemical ion gradient across the membrane. In vitro, all of these large protein complexes are able to use an ion gradient and the associated membrane potential to synthesize ATP. A-/F-/V-type ATPases are composed of two distinct segments: a catalytic sector, A1/F1/V1, whose three-dimensional structural relationship will be reviewed, and the membrane-embedded sector, Ao/Fo/Vo, which functions in ion conduction. Recent studies on the molecular biology of the Ao/Fo/Vo domains revealed surprising findings about duplicated and triplicated versions of the proteolipid subunit and shed new light on the evolution of these ion pumps. 相似文献
5.
Pingoud A Fuxreiter M Pingoud V Wende W 《Cellular and molecular life sciences : CMLS》2005,62(6):685-707
Type II restriction endonucleases are components of restriction modification systems that protect bacteria and archaea against invading foreign DNA. Most are homodimeric or tetrameric enzymes that cleave DNA at defined sites of 4–8 bp in length and require Mg2+ ions for catalysis. They differ in the details of the recognition process and the mode of cleavage, indicators that these enzymes are more diverse than originally thought. Still, most of them have a similar structural core and seem to share a common mechanism of DNA cleavage, suggesting that they evolved from a common ancestor. Only a few restriction endonucleases discovered thus far do not belong to the PD...D/ExK family of enzymes, but rather have active sites typical of other endonuclease families. The present review deals with new developments in the field of Type II restriction endonucleases. One of the more interesting aspects is the increasing awareness of the diversity of Type II restriction enzymes. Nevertheless, structural studies summarized herein deal with the more common subtypes. A major emphasis of this review will be on target site location and the mechanism of catalysis, two problems currently being addressed in the literature.Received 15 November 2004; accepted 9 December 2004 相似文献
6.
Structure, function and evolution of antifreeze proteins 总被引:16,自引:0,他引:16
Antifreeze proteins bind to ice crystals and modify their growth. These proteins show great diversity in structure, and they
have been found in a variety of organisms. The ice-binding mechanisms of antifreeze proteins are not completely understood.
Recent findings on the evolution of antifreeze proteins and on their structures and mechanisms of action have provided new
understanding of these proteins in different contexts. The purpose of this review is to present the developments in contrasting
research areas and unite them in order to gain further insight into the structure and function of the antifreeze proteins.
Received 2 September 1998; received after revision 21 October 1998; accepted 2 November 1998 相似文献
7.
Anti-DNA antibodies: aspects of structure and pathogenicity 总被引:4,自引:0,他引:4
Anti-DNA antibodies contribute to the pathology of systemic lupus erythematosus. Their depositon in tissue lesions could
result from localization of preformed immune complexes of antibodies with DNA or nucleosomes, or from cross-reaction of anti-DNA
antibodies directly with tissue proteins. Structural analyses contribute to understanding their pathogenic potential. Primary
structures of lupus immunoglobulin G double-stranded DNA-binding autoantibodies are determined by immunoglobulin genes with
mutated variable region segments, indicative of selection by immunizing antigen. Arginine, lysine and asparagine residues
in complementarity-determining region favor DNA binding. Heavy-chain variable regions make major contributions to DNA binding;
affinity and specificity of binding are modulated or can be abrogated by the light-chain variable domain. Crytallographic
structure is known for a few antibody-DNA complexes and several ligand-free Fab fragments. Computer modeling supplements this
limited information. Structural information of lupus antibody interactions with both DNA and cross-reacting molecules will
support use of ligands to inhibit tissue deposition of the antibodies and prevent lesion formation in lupus.
Received 4 July 2002; accepted 23 July 2002
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ID="*"Corresponding author. 相似文献
8.
M. Pucéat 《Cellular and molecular life sciences : CMLS》1999,55(10):1216-1229
Intracellular pH (pHi) is a major regulator of various and critical cellular functions. A close regulation of pHi is thus mandatory to maintain normal cellular activity. To this end, all cells express ion transporters that carry across
their plasma membrane H+ or equivalent H+ into and out of the cell. Besides pHi, these ion transporters are under the regulation of neurohormonal stimuli. This review summarises the molecular identity,
regulation and function of the main membrane pH-regulatory ion transporters.
Received 30 December 1998; received after revision 4 February 1999; accepted 9 February 1999 相似文献
9.
W. C. Wimsatt 《Archive for History of Exact Sciences》2012,66(4):359-396
A square tabular array was introduced by R. C. Punnett in (1907) to visualize systematically and economically the combination of gametes to make genotypes according to Mendel’s theory. This mode of representation evolved and rapidly became standardized as the canonical way of representing like problems in genetics. Its advantages over other contemporary methods are discussed, as are ways in which it evolved to increase its power and efficiency, and responded to changing theoretical perspectives. It provided a natural visual decomposition of a complex problem into a number of inter-related stages. This explains its computational and conceptual power, for one could simply “read off” answers to a wide variety of questions simply from the “right” visual representation of the problem, and represent multiple problems, and multiple layers of problems in the same diagram. I relate it to prior work on the evolution of Weismann diagrams by Griesemer and Wimsatt (What Philosophy of Biology Is, Martinus-Nijhoff, the Hague, 1989), and discuss a crucial change in how it was interpreted that midwifed its success. 相似文献
10.
Adducin: structure, function and regulation 总被引:7,自引:0,他引:7
Adducin is a ubiquitously expressed membrane-skeletal protein localized at spectrin-actin junctions that binds calmodulin and is an in vivo substrate for protein kinase C (PKC) and Rho-associated kinase. Adducin is a tetramer comprised of either alpha/beta or alpha/gamma heterodimers. Adducin subunits are related in sequence and all contain an N-terminal globular head domain, a neck domain and a C-terminal protease-sensitive tail domain. The tail domains of all adducin subunits end with a highly conserved 22-residue myristoylated alanine-rich C kinase substrate (MARCKS)-related domain that has homology to MARCKS protein. Adducin caps the fast-growing ends of actin filaments and also preferentially recruits spectrin to the ends of filaments. Both the neck and the MARCKS-related domains are required for these activities. The neck domain self-associates to form oligomers. The MARCKS-related domain binds calmodulin and contains the major phosphorylation site for PKC. Calmodulin, gelsolin and phosphorylation by the kinase inhibit in vitro activities of adducin involving actin and spectrin. Recent observations suggest a role for adducin in cell motility, and as a target for regulation by Rho-dependent and Ca2+-dependent pathways. Prominent physiological sites of regulation of adducin include dendritic spines of hippocampal neurons, platelets and growth cones of axons. 相似文献
11.
S.T.M. Allard M.-F. Giraud J.H. Naismith 《Cellular and molecular life sciences : CMLS》2001,58(11):1650-1665
Carbohydrates are ideally suited for molecular recognition. By varying the stereochemistry of the hydroxyl substituents, the simple six-carbon, six-oxygen pyranose ring can exist as 10 different molecules. With the further addition of simple chemical changes, the potential for generating distinct molecular recognition surfaces far exceeds that of amino acids. This ability to control and change the stereochemistry of the hydroxyl substituents is very important in biology. Epimerases can be found in animals, plants and microorganisms where they participate in important metabolic pathways such as the Leloir pathway, which involves the conversion of galactose to glucose-1-phosphate. Bacterial epimerases are involved in the production of complex carbohydrate polymers that are used in their cell walls and envelopes and are recognised as potential therapeutic targets for the treatment of bacterial infection. Several distinct strategies have evolved to invert or epimerise the hydroxyl substituents on carbohydrates. In this review we group epimerisation by mechanism and discuss in detail the molecular basis for each group. These groups include enzymes which epimerise by a transient keto intermediate, those that rely on a permanent keto group, those that eliminate then add a nucleotide, those that break then reform carbon-carbon bonds and those that linearize and cyclize the pyranose ring. This approach highlights the quite different biochemical processes that underlie what is seemingly a simple reaction. What this review shows is that each position on the carbohydrate can be epimerised and that epimerisation is found in all organisms. 相似文献
12.
Arabinogalactan-proteins: structure, expression and function 总被引:26,自引:0,他引:26
A.M. Showalter 《Cellular and molecular life sciences : CMLS》2001,58(10):1399-1417
Arabinogalactan-proteins (AGPs) are a family of extensively glycosylated hydroxyproline-rich glycoproteins that are thought to have important roles in various aspects of plant growth and development. After a brief introduction to AGPs highlighting the problems associated with defining and classifying this diverse family of glycoproteins, AGP structure is described in terms of the protein component (including data from molecular cloning), carbohydrate component, processing of AGPs (including recent data on glycosylphosphatidylinositol membrane anchors) and overall molecular shape. Next, the expression of AGPs is examined at several different levels, from the whole plant to the cellular levels, using a variety of experimental techniques and tools. Finally, AGP function is considered. Although the existing functional evidence is not incontrovertible, it does clearly point to roles for AGPs in vegetative, reproductive, and cellular growth and development as well as programmed cell death and social control. In addition and most likely inextricably linked to their functions, AGPs are presumably involved in molecular interactions and cellular signaling at the cell surface. Some likely scenarios are discussed in this context. AGPs also have functions of real or potential commercial value, most notably as emulsifiers in the food industry and as potential immunological regulators for human health. Several important questions remain to be answered with respect to AGPs. Clearly, elucidating the unequivocal functions of particular AGPs and relating these functions to their respective structures and modes of action remain as major challenges in the years ahead. 相似文献
13.
Viviani VR 《Cellular and molecular life sciences : CMLS》2002,59(11):1833-1850
Luciferases are the enzymes that catalyze the reactions that produce light in bioluminescence. Whereas the oxidative mechanism
which leads to light emission is similar for most luciferases, these enzymes and their substrates are evolutionarily unrelated.
Among all bioluminescent groups, insects constitute one of the most diverse in terms of biochemistry. In the fungus-gnats
(Mycetophilidae: Diptera), for example, bioluminescence is generated by two biochemically distinct systems. Despite the diversity,
investigations on insect luciferases and biochemistry have been conducted mostly with fireflies. The luciferases from the
related phengodid beetles, which can produce green to red bioluminescence using the same chemistry as firefly luciferases,
have been recently investigated. Beetle luciferases originated from ancestral acyl-CoA ligases. Present data suggest that
conserved motifs among this class of ligases are involved in substrate adenylation. The three-dimensional structure of firefly
luciferase was recently solved and mutagenesis studies have been performed identifying putative residues involved in luciferin
binding and bioluminescence color determination in several beetle luciferases. The knowledge gained through these studies
is helping in the development of useful reporter gene tools for biotechnological and biomedical purposes.
Received 4 March 2002; received after revision 13 May 2002; accepted 21 May 2002 相似文献
14.
Serine peptidases: Classification, structure and function 总被引:1,自引:1,他引:0
Serine peptidases play key roles in human health and disease and their biochemical properties shaped the molecular evolution
of these processes. Of known proteolytic enzymes, the serine peptidase family is the major cornerstone of the vertebrate degradome.
We describe the known diversity of serine peptidases with respect to structure and function. Particular emphasis is placed
on the S1 peptidase family, the trypsins, which underwent the most predominant genetic expansion yielding the enzymes responsible
for vital processes in man such as digestion, blood coagulation, fibrinolysis, development, fertilization, apoptosis and immunity.
Received 13 December 2007; received after revision 8 January 2008; accepted 22 January 2008 相似文献
15.
Inositol pyrophosphates: structure, enzymology and function 总被引:2,自引:0,他引:2
Christopher John Barker Christopher Illies Gian Carlo Gaboardi Per-Olof Berggren 《Cellular and molecular life sciences : CMLS》2009,66(24):3851-3871
The stereochemistry of the inositol backbone provides a platform on which to generate a vast array of distinct molecular motifs that are used to convey information both in signal transduction and many other critical areas of cell biology. Diphosphoinositol phosphates, or inositol pyrophosphates, are the most recently characterized members of the inositide family. They represent a new frontier with both novel targets within the cell and novel modes of action. This includes the proposed pyrophosphorylation of a unique subset of proteins. We review recent insights into the structures of these molecules and the properties of the enzymes which regulate their concentration. These enzymes also act independently of their catalytic activity via protein–protein interactions. This unique combination of enzymes and products has an important role in diverse cellular processes including vesicle trafficking, endo- and exocytosis, apoptosis, telomere length regulation, chromatin hyperrecombination, the response to osmotic stress, and elements of nucleolar function. 相似文献
16.
17.
Shikanai T 《Cellular and molecular life sciences : CMLS》2006,63(6):698-708
In plants, RNA editing is a process for converting a specific nucleotide of RNA from C to U and less frequently from U to
C in mitochondria and plastids. To specify the site of editing, the cis-element adjacent to the editing site functions as a binding site for the trans-acting factor. Genetic approaches using Arabidopsis thaliana have clarified that a member of the protein family with pentatricopeptide repeat (PPR) motifs is essential for RNA editing
to generate a translational initiation codon of the chloroplast ndhD gene. The PPR motif is a highly degenerate unit of 35 amino acids and appears as tandem repeats in proteins that are involved
in RNA maturation steps in mitochondria and plastids. The Arabidopsis genome encodes approximately 450 members of the PPR family, some of which possibly function as trans-acting factors binding the cis-elements of the RNA editing sites to facilitate access of an unidentified RNA editing enzyme. Based on this breakthrough
in the research on plant RNA editing, I would like to discuss the possible steps of co-evolution of RNA editing events and
PPR proteins.
Received 30 September 2005; received after revision 5 November 2005; accepted 28 November 2005 相似文献
18.
19.
M. Nguyen-Distèche C. Fraipont N. Buddelmeijer N. Nanninga 《Cellular and molecular life sciences : CMLS》1998,54(4):309-316
Escherichia coli penicillin-binding protein PBP3 is a key element in cell septation. It is presumed to catalyse a transpeptidation reaction during biosynthesis of the septum peptidoglycan but, in vitro, its enzymatic activity has only been demonstrated with thiolester analogues of the natural peptide substrate. It has no detectable transglycosylase activity with lipid II as substrate. This tripartite protein is constructed of an N-terminal membrane anchor-containing module that is essential for cell septation, a non-penicillin-binding (n-PB) module of unknown function and a C-terminal penicillin-binding (PB) module exhibiting all the characteristic motifs of penicilloyl serine transferases. The n-PB module, which is required for the folding and stability of the PB module, may provide recognition sites for other cell division proteins. Initiation of septum formation is not PBP3-dependent but rests on the appearance of the FtsZ ring, and is thus penicillin-insensitive. The control of PBP3 activity during the cell cycle is briefly discussed. 相似文献
20.
Platelet-activating factor acetylhydrolases (PAF-AHs, EC 3.1.1.47) constitute a unique and biologically important family of phospholipase A2s. They are related to neither the well-characterized secretory nor cytosolic PLA2s, and unlike them do not require Ca2+ for catalytic activity. The distinguishing property of PAF-AHs is their unique substrate specificity they act on the phospholipid platelet-activating factor (PAF), and in some cases on proinflammatory polar phospholipids, from which they remove a short acyl moiety – acetyl in the case of PAF – located at the sn-2 position. Because PAF is found both in the plasma and in the cytosol of many tissues, PAF-acetylhydrolases are equally widely distributed in an animal organism. Recent crystallographic studies shed new light on the complex structure-function relationships in PAF-AHs. Received 15 September 1997; received after revision 23 February 1998; accepted 25 February 1998 相似文献