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1.
The evolutionary relationships of ribosomal proteins from eubacteria, archaea, eukaryotes, chloroplasts and mitochondria
were examined by their degree of conservation, their structural and functional properties and by the occurrence of conserved
structural elements. The structural domains formed by the different protein families were studied. The occurrence of monophyletic
groups was investigated for each protein family within the archaea. Phylogenetic trees were constructed between these organisms
and together with the homologous sequences of the other phylogenetic domains. All organisms belonging to the archaea clearly
formed a monophyletic group. The conserved sequence motifs were checked for the potential to form similar secondary structural
elements.
Received 24 October 1996; accepted 30 October 1996 相似文献
2.
Zinc plays an important role in the structure and function of many enzymes, including alcohol dehydrogenases (ADHs) of the
MDR type (mediumchain dehydrogenases/reductases). Active site zinc participates in catalytic events, and structural site zinc
maintains structural stability. MDR-types of ADHs have both of these zinc sites but with some variation in ligands and spacing.
The catalytic zinc sites involve three residues with different spacings from two separate protein segments, while the structural
zinc sites involve four residues and cover a local segment of the protein chain (Cys97-Cys111 in horse liver class I ADH).
This review summarizes properties of both ADH zinc sites, and relates them to zinc sites of proteins in general. In addition,
it highlights a separate study of zinc binding peptide variants of the horse liver ADH structural zinc site. The results show
that zinc coordination of the free peptide differs markedly from that of the enzyme (one His / three Cys versus four Cys),
suggesting that the protein zinc site is in an energetically strained conformation relative to that of the peptide. This finding
is a characteristic of an entatic state, implying a functional nature for this zinc site. 相似文献
3.
Hiraiwa M 《Cellular and molecular life sciences : CMLS》1999,56(11-12):894-907
Cathepsin A/protective protein [3.4.16.5], carboxypeptidase A, is a lysosomal serine protease with structural homology to yeast (Saccharomyces cerevisiae) carboxypeptidase Y. Cathepsin A is a member of the alpha/beta hydrolase fold family and has been suggested to share a common ancestral relationship with other alpha/beta hydrolase fold enzymes, such as cholinesterases. Several lines of evidence indicate that cathepsin A is a multicatalytic enzyme with deamidase and esterase in addition to carboxypeptidase activities. Cathepsin A was recently identified in human platelets as deamidase. In vitro, it hydrolyzes a variety of bioactive peptide hormones including tachykinins, suggesting that extralysosomal cathepsin A plays a role in regulation of bioactive peptide functions. Recent reports emphasize the lysosomal protective function of cathepsin A rather than its protease function. The protective function of cathepsin A is distinct from its catalytic function. Human lysosomal beta-galactosidase and neuraminidase exist as a high molecular weight enzyme complex, in which there is a 54-kDa glycoprotein termed 'lysosomal protective protein'. Based on cell culture studies, protective protein was found to protect both beta-galactosidase and neuraminidase from intralysosomal proteolysis by forming a multienzyme complex and was shown to be deficient in patients with galactosialidosis, a combined deficiency of beta-galactosidase and neuraminidase. Molecular cloning and gene expression studies have disclosed that protective protein is cathepsin A. The cathepsin A precursor has the potential to restore both beta-galactosidase and neuraminidase activities in fibroblasts from patients with galactosialidosis. Cathepsin A knockout mice showed a phenotype similar to human galactosialidosis and the deficient phenotype found in the mutant mice was corrected by transplanting erythroid precursor cells overexpressing cathepsin A. Collectively, these findings demonstrate the significance of cathepsin A as a key molecule in the onset of galactosialidosis and also highlight the therapeutic potential of the cathepsin A precursor for patients with galactosialidosis. 相似文献
4.
Tse Siang Kang R. Manjunatha Kini 《Cellular and molecular life sciences : CMLS》2009,66(14):2341-2361
The last several decades have seen an explosion of knowledge in the field of structural biology. With critical advances in spectroscopic techniques in examining structures of biomacromolecules, in maturation of molecular biology techniques, as well as vast improvements in computation prowess, protein structures are now being elucidated at an unprecedented rate. In spite of all the recent advances, the protein folding puzzle remains as one of the fundamental biochemical challenges. A facet to this empiric problem is the structural determinants of protein folding. What are the driving forces that pivot a polypeptide chain to a specific conformation amongst the vast conformation space? In this review, we shall discuss some of the structural determinants to protein folding that have been identified in the recent decades. 相似文献
5.
Daniel Kümmel Julia Walter Martin Heck Udo Heinemann Michael Veit 《Cellular and molecular life sciences : CMLS》2010,67(15):2653-2664
Bet3, a transport protein particle component involved in vesicular trafficking, contains a hydrophobic tunnel occupied by
a fatty acid linked to cysteine 68. We reported that Bet3 has a unique self-palmitoylating activity. Here we show that mutation
of arginine 67 reduced self-palmitoylation of Bet3, but the effect was compensated by increasing the pH. Thus, arginine helps
to deprotonate cysteine such that it could function as a nucleophile in the acylation reaction which is supported by the structural
analysis of non-acylated Bet3. Using fluorescence spectroscopy we show that long-chain acyl-CoAs bind with micromolar affinity
to Bet3, whereas shorter-chain acyl-CoAs do not interact. Mutants with a deleted acylation site or a blocked tunnel bind to
Pal-CoA, only the latter with slightly reduced affinity. Bet3 contains three binding sites for Pal-CoA, but their number was
reduced to two in the mutant with an obstructed tunnel, indicating that Bet3 contains binding sites on its surface. 相似文献
6.
Alcohols affect a wide array of biological processes including protein folding, neurotransmission and immune responses. It is becoming clear that many of these effects are mediated by direct binding to proteins such as neurotransmitter receptors and signaling molecules. This review summarizes the unique chemical properties of alcohols which contribute to their biological effects. It is concluded that alcohols act mainly as hydrogen bond donors whose binding to the polypeptide chain is stabilized by hydrophobic interactions. The electronegativity of the O atom may also play a role in stabilizing contacts with the protein. Properties of alcohol binding sites have been derived from X-ray crystal structures of alcohol-protein complexes and from mutagenesis studies of ion channels and enzymes that bind alcohols. Common amino acid sequences and structural features are shared among the protein segments that are involved in alcohol binding. The alcohol binding site is thought to consist of a hydrogen bond acceptor in a turn or loop region that is often situated at the N-terminal end of an alpha-helix. The methylene chain of the alcohol molecule appears to be accommodated by a hydrophobic groove formed by two or more structural elements, frequently a turn and an alpha-helix. Binding at these sites may alter the local protein structure or displace bound solvent molecules and perturb the function of key proteins. 相似文献
7.
Biochemical characterization and bacterial expression of an odorant-binding protein from <Emphasis Type="Italic">Locusta migratoria</Emphasis> 总被引:1,自引:0,他引:1
Ban L Scaloni A D'Ambrosio C Zhang L Yahn Y Pelosi P 《Cellular and molecular life sciences : CMLS》2003,60(2):390-400
Analysis of soluble proteins from different body parts of Locusta migratoria revealed a fast-migrating component in native electrophoresis, unique to antennae of both sexes. N-terminal sequence analysis and cloning identified this protein as a member of the insect odorant-binding proteins, carrying a well-conserved six-cysteine motif. Mass spectrometry analysis confirmed the occurrence of two distinct polypeptide species determined by nucleotide sequencing and demonstrated that the cysteine residues are paired in an interlocked fashion. The protein was expressed in a bacterial system with yields of about 10 mg/l of culture, mostly present as inclusion bodies. However, this recombinant product was solubilized after disulfide reduction. Air oxidation yielded a species with all disulfides spontaneously formed as in the native counterpart. Both native and recombinant proteins migrated as a dimer in gel filtration chromatography. Ligand binding was measured, using N-phenyl-1-naphthylamine as the fluorescent probe; the affinity of other ligands was measured in competitive binding assays. The protein exhibited great resistance to thermal denaturation even following prolonged treatment at 100 degrees C. A structural model for this dimeric species was generated on the basis of its sequence homology with Bombyx mori pheromone-binding protein, whose three-dimensional structure has been resolved as an unbound species and in complex with its physiological ligand. This is the first report of an odorant-binding protein identified and characterized from Orthoptera. 相似文献
8.
Cowan-Jacob SW 《Cellular and molecular life sciences : CMLS》2006,63(22):2608-2625
Our current understanding of the structure, mechanism of action and modes of regulation of the protein tyrosine kinase family
owes a great deal to structural biology. Structures are now available for more than 20 different tyrosine kinase domains,
many of these in multiple conformational states. They form the basis for the design of experiments to further investigate
the role of different structural elements in the normal function and regulation of the protein and in the pathogenesis of
many human diseases. Once thought to be too similar to be specifically inhibited by a small molecule, structural differences
between kinases allow the design of compounds which inhibit only an acceptable few. This review gives a general overview of
protein tyrosine kinase structural biology, including a discussion of the strengths and limitations of the investigative methods
involved.
Received 2 May 2006; received after revision 21 June 2006; accepted 9 August 2006 相似文献
9.
Teemu Haikarainen Anastassios C. Papageorgiou 《Cellular and molecular life sciences : CMLS》2010,67(3):341-351
Dps-like proteins are key factors involved in the protection of prokaryotic cells from oxidative damage. They act by either
oxidizing iron to prevent the formation of oxidative radicals or by forming Dps-DNA complexes to physically protect DNA. All
Dps-like proteins are characterized by a common three-dimensional architecture and are found as spherical dodecamers with
a hollow central cavity. Despite their structural similarities, recent biochemical and structural data have suggested different
functions among members of the family that range from protection inside the cells in response to various stress signals to
adhesion and virulence during bacterial infections. Moreover, the Dps-like proteins have lately attracted considerable interest
in the field of nanotechnology owing to their ability to act as protein cages for iron and various other metals. A better
understanding of their function and mechanism could therefore lead to novel applications in biotechnology and nanotechnology. 相似文献
10.
The Rh (Rhesus) genes encode a family of conserved proteins that share a structural fold of 12 transmembrane helices with
members of the major facilitator superfamily. Interest in this family has arisen from the discovery of Rh factor’s involvement
in hemolytic disease in the fetus and newborn, and of its homologs widely expressed in epithelial tissues. The Rh factor and
Rh-associated glycoprotein (RhAG), with epithelial cousins RhBG and RhCG, form four subgroups conferring upon vertebrates
a genealogical commonality. The past decade has heralded significant advances in understanding the phylogenetics, allelic
diversity, crystal structure, and biological function of Rh proteins. This review describes recent progress on this family
and the molecular insights gleaned from its gene evolution, membrane biology, and disease association. The focus is on its
long evolutionary history and surprising structural conservation from prokaryotes to humans, pointing to the importance of
its functional role, related to but distinct from ammonium transport proteins. 相似文献
11.
The polypyrimidine tract binding protein (PTB) is a 58-kDa RNA binding protein involved in multiple aspects of mRNA metabolism
including splicing regulation, polyadenylation, 3′end formation, internal ribosomal entry site-mediated translation, RNA localization
and stability. PTB contains four RNA recognition motifs (RRMs) separated by three linkers. In this review we summarize structural
information on PTB in solution that has been gathered during the past 7 years using NMR spectroscopy and small-angle X-ray
scattering. The structures of all RRMs of PTB in their free state and in complex with short pyrimidine tracts, as well as
a structural model of PTB RRM2 in complex with a peptide, revealed unusual structural features that provided new insights
into the mechanisms of action of PTB in the different processes of RNA metabolism and in particular splicing regulation.
Received 16 August 2007; received after revision 18 September 2007; accepted 2 October 2007 相似文献
12.
H. Van Dael 《Cellular and molecular life sciences : CMLS》1998,54(11):1217-1230
Protein folding is an extremely active field of research where biology, chemistry, computer science and physics meet. Although
the study of protein-folding intermediates in general and equilibrium intermediates in particular has grown considerably in
recent years, many questions regarding the conformational state and the structural features of the various partially folded
intermediate states remain unanswered. Performing kinetic measurements on proteins that have had their structures modified
by site-directed mutagenesis, the so-called protein-engineering method, is an obvious way to gain fine structural information.
In the present review, this method has been applied to a variety of proteins belonging to the lysozyme/α-lactalbumin family. Besides recombinants obtained by point mutations of individual critical residues, chimeric proteins in
which whole structural elements (10 – 25 residues) from α-lactalbumin were inserted into a human lysozyme matrix are examined. The conformational properties of the equilibrium intermediate
states are discussed together with the structural characterization of the partially unfolded states encountered in the kinetic
folding pathway.
Received 28 May 1998; received after revision 6 July 1998; accepted 6 July 1998 相似文献
13.
The spliceosome is a dynamic macromolecular machine that catalyzes pre-mRNA splicing through a mechanism controlled by several accessory proteins, including the Dim proteins. The Dim protein family is composed of two classes, Dim1 and Dim2, which share a common thioredoxin-like fold. They were originally identified for their role in cell cycle progression and have been found to interact with Prp6, an essential component of the spliceosome, which forms the bridge of U4/U6.U5-tri-snRNP. In spite of their biological and structural similarities, Dim1 and Dim2 proteins differ in many aspects. Dim1 bears distinctive structural motifs responsible for its interaction with other spliceosome components. Dim2 forms homodimers and contains specific domains required for its interactions with partners. This originality suggests that although both proteins are involved in pre-mRNA splicing, they are likely to be involved in different biological pathways. In the present article we review the structure and function of the Dim proteins. 相似文献
14.
Mornon JP Prat K Dupuis F Callebaut I 《Cellular and molecular life sciences : CMLS》2002,59(8):1366-1376
Animal prion proteins (PrPs) form at the sequence level a very homogenous and 'closed' family. Therefore, few of their structural and functional features can be gleaned from sequence comparison as is now possible on a wide scale for other protein families. To detect putatively related proteins (at the structural and/or functional level), we used a battery of sequence analysis tools. This analysis resulted in (i) the identification of a putative 'prion-like' domain within the envelope of foamy retroviruses, (ii) the detection of putative similarities between prions and an interferon-inducible membrane protein, and (iii) the proposal that of the TATA-box-binding protein is a structural scaffold, which might allow understanding of a key event leading to the structural conversion from PrP(C) (normal cellular prion structure) towards PrP(Sc) (pathogenic structure). 相似文献
15.
Protein synthesis is one of the most complex cellular processes, involving numerous translation components that interact in multiple sequential steps. The most complex stage in protein synthesis is the initiation process. It involves initiation factor-mediated assembly of a 40S ribosomal subunit and initiator tRNA into a 48S initiation complex at the initiation codon of an mRNA and subsequent joining of a 60S ribosomal subunit to form a translationally active 80S ribosome. The basal set of factors required for translation initiation has been determined, and biochemical, genetic, and structural studies are now beginning to reveal details of their individual functions in this process. The mechanism of translation initiation has also been found to be influenced significantly by structural properties of the 5' and 3' termini of individual mRNAs. This review describes some of the major developments in elucidating molecular details of the mechanism of initiation that have occurred over the last decade. 相似文献
16.
H. W. Hofer 《Cellular and molecular life sciences : CMLS》1996,52(5):449-454
The glycolytic control enzyme phosphofructokinase from the parasitic nematodeAscaris lumbricodies is regulated by reversible phosphorylation. The enzyme is phosphorylated by an atypical cyclic adenosine monophosphate (cAMP)-dependent protein kinase whose substrate specificity deviates from that of the mammalian protein kinase. This variation is explained by structural peculiarities on the surface part of the catalytic groove of the protein kinase. Also, the protein phosphatases responsible for the reversal of phosphorylation appear to act specifically in glycolysis and are different from those participating in regulation of glycogenolysis. 相似文献
17.
In this report we describe the main features of the initially determined alcohol dehydrogenase, that of horse liver, relate
this to the human enzyme structures and review recent structural studies on mutants and new complexes of the enzymes. We further
review the structure of a bacterial alcohol dehydrogenase to arrive at a coherent picture of medium-chain dehydrogenase/reductase
alcohol dehydrogenases in general. 相似文献
18.
This review outlines the use of expressed protein ligation (EPL) to study protein structure, function and stability. EPL is a chemoselective ligation method that allows the selective ligation of unprotected polypeptides from synthetic and recombinant origin for the production of semi-synthetic protein samples of well-defined and homogeneous chemical composition. This method has been extensively used for the site-specific introduction of biophysical probes, unnatural amino acids, and increasingly complex post-translational modifications. Since it was introduced 10 years ago, EPL applications have grown increasingly more sophisticated in order to address even more complex biological questions. In this review, we highlight how this powerful technology combined with standard biochemical analysis techniques has been used to improve our ability to understand protein structure and function. 相似文献
19.
P. S. Chen 《Cellular and molecular life sciences : CMLS》1976,32(5):549-551
Summary Electrophoretic analysis of the soluble proteins in the paragonial glands of 11Drosophila species demonstrated that the patterns are highly species-specific. The possible functional significance of these proteins is discussed.This work was supported by grants from the Schweizerischer Nationalfonds and the Georges und Antoine Claraz-Schenkung. 相似文献
20.
Site- and state-specific lysine methylation of histones is catalyzed by a family of proteins that contain the evolutionarily
conserved SET domain and plays a fundamental role in epigenetic regulation of gene activation and silencing in all eukaryotes.
The recently determined three-dimensional structures of the SET domains from chromosomal proteins reveal that the core SET
domain structure contains a two-domain architecture, consisting of a conserved anti-parallel β-barrel and a structurally variable
insert that surround a unusual knot-like structure that comprises the enzyme active site. These structures of the SET domains,
either in the free state or when bound to cofactor S-adenosyl-L-homocysteine and/or histone peptide, mimicking an enzyme/cofactor/substrate complex, further yield the structural insights
into the molecular basis of the substrate specificity, methylation multiplicity and the catalytic mechanism of histone lysine
methylation.
Received 10 June 2006; accepted 22 August 2006 相似文献