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1.
The cleavage of dynorphin and three analogs containing paired basic residues by several proteases was investigated. The cysteine protease of neuroblastoma cells cleaved only the bond between Arg-Arg residues. Submandibular arginyl-endopeptidase, however, cleaved bonds between both Arg-Arg and Arg-Lys residues, and pancreatic trypsin at the carboxyl sides of both arginine and lysine residues. This shows that the cysteine protease is highly specific for paired arginine residues. 相似文献
2.
Herrmann A Svangård E Claeson P Gullbo J Bohlin L Göransson U 《Cellular and molecular life sciences : CMLS》2006,63(2):235-245
Cyclotides are cyclic plant proteins with potent cytotoxic effects. Here we systematically probed the importance of surface-exposed
charged amino acid residues of the cyclotide cycloviolacin O2, using a strategy involving chemical modifications. We show
that the single glutamic acid plays a key role for the cytotoxicity: methylation of this residue produced a 48-fold decrease
in potency. Virtually no change in potency was observed when masking the single arginine residue using 1,2-cyclohexanedione,
while acetylation of the two lysine residues reduced the potency 3-fold. The derivative with modifications at both arginine
and lysine residues showed a 7-fold loss of potency. In addition, we show that the activity is dependent on an intact disulfide
network and that the short sequences between the six cysteine residues, that is, the backbone loops, are devoid of cytotoxic
activity.
Received 11 October 2005; received after revision 3 November 2005; accepted 15 November 2005 相似文献
3.
Structural modification studies have been shown that a cysteine, a histidine and possibly an arginine residue are involved in the catalytic process. The enzyme gave a single band on polyacrylamide gel electrophoresis, and the amino acid analysis showed it to contain a high proportion of hydrophobic residues, which was in agreement with the chemical modification results. 相似文献
4.
Sylvia Yergatian J. B. Lee M. J. Geisow J. C. Ireson 《Cellular and molecular life sciences : CMLS》1977,33(12):1570-1571
Summary Structural modification studies have shown that a cysteine, a histidine and possibly an arginine residue are involved in the catalytic process. The enzyme gave a single band on polyacrylamide gel electrophoresis, and the amino acid analysis showed it to contain a high proportion of hydrophobic residues, which was in agreement with the chemical modification results.Acknowledgment. We wish to thank Herts CC for a research assistantship (S.Y.) and SRC for a research fellowship (to M.J.G.) 相似文献
5.
Trefoil factors 总被引:7,自引:0,他引:7
The present review will include the mammalian trefoil factors, TFF1, TFF2 and TFF3. It will summarise the amino acid sequences from different species, their posttranslational modifications and their structures determined by X-ray analysis and nuclear magnetic resonance studies. Trefoil factors all have a well-defined, structurally conserved trefoil domain. The trefoil domain consists of 42 or 43 amino acid residues and contains 6 cysteine residues that form disulphide bonds in a 1-5, 2-4 and 3-6 configuration. By the establishment of an additional intra-molecular disulphide bond at the C-terminal end, TFF1 and TFF3 form homodimers or heterodimers. This dimer formation of TFF1 and TFF3 will be discussed, and the possible implications for biological activity will be reviewed. The physicochemical characteristics including protease stability of trefoil factors will be summarised. The biological implications of different molecular forms of trefoil factors and their interaction with mucins will be discussed together with other functional insights. 相似文献
6.
The focus of this review is the M-superfamily of Conus venom peptides. Disulfide rich peptides belonging to the M-superfamily have three loop regions and the cysteine arrangement:
CC–C–C–CC, where the dashes represent loops one, two, and three, respectively. Characterization of M-superfamily peptides
has demonstrated that diversity in cystine connectivity occurs between different branches of peptides even though the cysteine
pattern remains consistent. This superfamily is subdivided into five branches, M-1 through M-5, based on the number of residues
in the third loop region, between the fourth and fifth cysteine residues. M-superfamily peptides appear to be ubiquitous in
Conus venom. They are largely unexplained in indigenous biological function, and they represent an active area of research within
the scientific community. 相似文献
7.
Dubin G 《Cellular and molecular life sciences : CMLS》2005,62(6):653-669
Studies of proteinaceous cysteine protease inhibitors originated with the discovery of cystatins in the 1960s. Since that time, a rich and fascinating world of proteins that control and regulate a multitude of important physiological processes, ranging from the basics of protein turnover to development and brain function, has been uncovered. Failures in such important and complex systems inevitably lead to pathologies. Many threatening diseases such as cancer or neurological disorders, to mention only some, are attributed to deregulation of proteaseinhibitor balance. Moreover, important aspects of infection pathology and host defense rely on proteolysis and protease inhibition. Recent advances in the field of protease inhibitors have drawn attention to the possible use of this collected knowledge to control related pathological processes. This review attempts to familiarize the reader with proteinaceous cysteine protease inhibitors by providing an overview of current knowledge. The work primarily highlights biological processes in which the inhibitors are involved and focuses on pathologies resulting from aberrant protease-inhibitor balance, pointing out emerging possibilities for their correction.Received 11 October 2004; received after revision 29 November 2004; accepted 6 December 2004 相似文献
8.
The arginine-specific reagent phenylglyoxal rapidly inactives glutamic decarboxylase from both mouse brain and E. coli when preincubated with the enzyme at concentrations of 3 mM to 40 mM. The rate of inactivation follows pseudo-first-order kinetics and is dependent upon the concentration of phenylglyoxal. These and other data presented support the idea that arginine residues play a key role in the mechanism of action of glutamic decarboxylase. 相似文献
9.
Juste Wesche Sarah Kühn Benedikt M. Kessler Maayan Salton Alexander Wolf 《Cellular and molecular life sciences : CMLS》2017,74(18):3305-3315
Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues. The reversibility of histone modifications is an essential feature of epigenetic regulation to respond to changes in environmental factors, signalling events, or metabolic alterations. Prominent histone modifications like lysine acetylation and lysine methylation are reversible. Enzyme family pairs have been identified, with each pair of lysine acetyltransferases/deacetylases and lysine methyltransferases/demethylases operating complementarily to generate or erase lysine modifications. Several analyses also indicate a reversible nature of arginine methylation, but the enzymes facilitating direct removal of methyl moieties from arginine residues in proteins have been discussed controversially. Differing reports have been seen for initially characterized putative candidates, like peptidyl arginine deiminase 4 or Jumonji-domain containing protein 6. Here, we review the most recent cellular, biochemical, and mass spectrometry work on arginine methylation and its reversible nature with a special focus on putative arginine demethylases, including the enzyme superfamily of Fe(II) and 2-oxoglutarate-dependent oxygenases. 相似文献
10.
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
11.
Summary The arginine-specific reagent phenylglyoxal rapidly inactives glutamic decarboxylase from both mouse brain andE. coli when preincubated with the enzyme at concentrations of 3 mM to 40 mM. The rate of inactivation follows pseudo-first-order kinetics and is dependent upon the concentration of phenylglyoxal. These and other data presented support the idea that arginine residues play a key role in the mechanism of action of glutamic decarboxylase. 相似文献
12.
Izuhara K Ohta S Kanaji S Shiraishi H Arima K 《Cellular and molecular life sciences : CMLS》2008,65(16):2541-2553
The inhibitory mechanism against proteases is important in the maintenance of homeostasis or health in the body. The human ovalbumin serpin (ovserpin)/ clade B serpin family is one group of the human serpins, a family of serine protease inhibitors. They have acquired diversity in the profiles of target proteases, inhibitory mechanisms, and localization patterns during their evolution. Most serpins target serine proteases, however, some ov-serpins target only cysteine proteases or both serine and cysteine proteases and furthermore, several ov-serpins do not possess inhibitory activities. Although the ov-serpins act primarily as intracellular serpins, some show extracellular and nuclear localizations. Such diversity enables the ov-serpins to play multiple physiological roles in the body. Recent analyses have revealed that the functions of human ov-serpins are more diversified than we previously knew. In this article, we describe recent progress in our understanding of how the human ov-serpin/clade B serpin family demonstrates diversity. 相似文献
13.
Proline-rich antimicrobial peptides are a group of cationic host defense peptides of vertebrates and invertebrates characterized
by a high content of proline residues, often associated with arginine residues in repeated motifs. Those isolated from some
mammalian and insect species, although not evolutionarily related, use a similar mechanism to selectively kill Gram-negative
bacteria, with a low toxicity to animals. Unlike other types of antimicrobial peptides, their mode of action does not involve
the lysis of bacterial membranes but entails penetration into susceptible cells, where they then act intracellularly. Some
aspects of the transport system and cytoplasmic targets have been elucidated. These features make them attractive both as
anti-infective lead compounds and as a new class of potential cell-penetrating peptides capable of internalising membrane-impermeant
drugs into both bacterial and eukaryotic cells 相似文献
14.
F. Magherini A. Carpentieri A. Amoresano T. Gamberi C. De Filippo L. Rizzetto M. Biagini P. Pucci A. Modesti 《Cellular and molecular life sciences : CMLS》2009,66(5):933-947
In this study, a proteomic approach that combines selective labelling of proteins containing reduced cysteine residues with
two-dimensional electrophoresis/mass spectrometry was used to evaluate the redox state of protein cysteines during chronological
ageing in Saccharomyces cerevisiae. The procedure was developed on the grounds that biotinconjugated iodoacetamide (BIAM) specifically reacts with reduced cysteine
residues. BIAM-labelled proteins can then be selectively isolated by streptavidin affinity capture. We compared cells grown
on 2% glucose in the exponential phase and during chronological ageing and we found that many proteins undergo cysteine oxidation.
The target proteins include enzymes involved in glucose metabolism. Both caloric restriction and growth on glycerol resulted
in a decrease in the oxidative modification. Furthermore, in these conditions a reduced production of ROS and a more negative
glutathione half cell redox potential were observed.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 15 September 2008; received after revision 17 December 2008; accepted 06 January 2009 相似文献
15.
Rike Wallbrecher Wouter P. R. Verdurmen Samuel Schmidt Petra H. Bovee-Geurts Felix Broecker Anika Reinhardt Toin H. van Kuppevelt Peter H. Seeberger Roland Brock 《Cellular and molecular life sciences : CMLS》2014,71(14):2717-2729
Binding to negatively charged heparan sulfates (HS) at the cell surface is considered the first step in the internalization of cationic cell-penetrating peptides (CPPs). However, little is known about the relation of the characteristics of the HS-CPP interaction such as affinity, stoichiometry, and clustering with uptake. In this study, we investigated a collection of mutants of a cyclic CPP derived from human lactoferrin with respect to HS binding and uptake. The thermodynamic parameters of HS binding were determined by isothermal titration calorimetry, clustering of HS was investigated by dynamic light scattering, and cellular uptake by flow cytometry and confocal microscopy. Whereas mutations of non-arginine amino acids that are conserved across lactoferrins of different mammalia only had a minor effect on uptake efficiency, changes in the number of arginine residues influenced the uptake significantly. In general, introduction of arginine residues and cyclization improved the HS affinity and the ability to cluster HS. In particular, there was a strong negative correlation between stoichiometry and uptake, indicating that crosslinking of HS is the driving force for the uptake of arginine-rich CPPs. Using glycan microarrays presenting a collection of synthetic HS, we show that a minimal chain length of HS is required for peptide binding. 相似文献
16.
Epigenetic mechanisms in mammals 总被引:11,自引:1,他引:10
DNA and histone methylation are linked and subjected to mitotic inheritance in mammals. Yet how methylation is propagated
and maintained between successive cell divisions is not fully understood. A series of enzyme families that can add methylation
marks to cytosine nucleobases, and lysine and arginine amino acid residues has been discovered. Apart from methyltransferases,
there are also histone modification enzymes and accessory proteins, which can facilitate and/or target epigenetic marks. Several
lysine and arginine demethylases have been discovered recently, and the presence of an active DNA demethylase is speculated
in mammalian cells. A mammalian methyl DNA binding protein MBD2 and de novo DNA methyltransferase DNMT3A and DNMT3B are shown experimentally to possess DNA demethylase activity. Thus, complex mammalian
epigenetic mechanisms appear to be dynamic yet reversible along with a well-choreographed set of events that take place during
mammalian development. 相似文献
17.
Mukhopadhyay A Ni L Yang CS Weiner H 《Cellular and molecular life sciences : CMLS》2005,62(16):1890-1899
Phage display was used to identify new components of the mammalian mitochondrial receptor complex using Tom20 as a binding partner. Two peptides were identified. One had partial identity (SMLTVMA) with a bacterial signal peptide from Toho-1, a periplasmic protein. The other had partial identity with a mitochondrial inner membrane glutamate carrier. The bacterial signal peptide could carry a protein into mitochondria both in vivo and in vitro. The first six residues of the sequence, SMLTVM, were necessary for import but the two adjacent arginine residues in the 30-amino-acid leader were not critical for import. The signal peptides of Escherichia coli β-lactamase and Bacillsus subtilis lipase could not carry proteins into mitochondria. Presumably, the Toho-1 leader can adopt a structure compatible for recognition by the import apparatus.Received 29 April 2005; received after revision 8 June 2005; accepted 17 June 2005 相似文献
18.
Immunomodulatory properties of cystatins 总被引:8,自引:0,他引:8
Cystatins are natural tight-binding reversible inhibitors of cysteine proteases. Because these cysteine proteases exist in
all living organisms and because they are involved in various biological and pathological processes, the control of these
protease functions by cystatins is of cardinal importance. Cystatins are found in mammals but cystatin-like molecules are
also present in mammals and parasites. In the immune system, cystatins modulate cathepsin activities and antigen presentation.
They also induce tumor necrosis factor α and interleukin 10 synthesis, and they stimulate nitric oxide production by interferon
γ-activated murine macrophages. In turn, nitric oxide has inhibitory activity on cysteine proteases, especially those from
parasitic protozoa. Cystatins isolated from parasitic nematodes also have immunomodulatory activities that are distinguishable
from those induced by lipopolysacharide-like molecules from endosymbiotic bacteria. On the whole, cystatins and cystatin-like
molecules belong to a new category of immunomodulatory molecules. Doubtless increasing data will improve our knowledge of
this property, leading to practical applications in immunotherapy.
Received 11 April 2002; accepted 18 April 2002
RID="*"
ID="*"Corresponding author. 相似文献
19.
Protein C inhibitor (PCI) is a widely distributed, multifunctional member of the serpin family of protease inhibitors, and
has been implicated in several physiological processes and disease states. Its inhibitory activity and specificity are regulated
by binding to cofactors such as heparin, thrombomodulin and phospholipids, and it also appears to have non-inhibitory functions
related to hormone and lipid binding. Just how the highly conserved serpin architecture can support the multiple diverse functions
of PCI is a riddle best addressed by protein crystallography. Over the last few years we have solved the structure of PCI
in its native, cleaved and protein-complexed states. They reveal a conserved serpin fold and general mechanism of protease
inhibition, but with some unique features relating to inhibitory specificity/promiscuity, cofactor binding and hydrophobic
ligand transport.
Received 1 July 2008; received after revision 16 August 2008; accepted 22 August 2008 相似文献
20.
Unique evolution of Bivalvia arginine kinases 总被引:1,自引:0,他引:1
Takeuchi M Mizuta C Uda K Fujimoto N Okamoto M Suzuki T 《Cellular and molecular life sciences : CMLS》2004,61(1):110-117
The clams Pseudocardium, Solen, Corbicula and Ensis possess a unique form of arginine kinase (AK) with a molecular mass of 80 kDa and an unusual two-domain structure, a result of gene duplication and subsequent fusion. These AKs also lack two functionally important amino acid residues, Asp62 and Arg193, which are strictly conserved in other 40-kDa AKs and are assumed to be key residues for stabilizing the substrate-bound structure. However, these AKs show higher enzyme activity. The cDNA-derived amino acid sequences of 40-kDa AKs from the blood clam Scapharca broughtonii and the oyster Crassostrea gigas were determined. While Asp62 and Arg193 are conserved in Scapharca AK, these two key residues are replaced by Asn and Lys, respectively, in Crassostrea AK. The native enzyme from Crassostrea and both of the recombinant enzymes show an enzyme activity similar to that of two-domain clam AKs and at least twofold higher than that of other molluskan AKs. Although the replacement of Asp62 or Arg193 by Gly in normal AK causes a considerable decrease in Vmax (6–15% of wild-type enzyme) and a two- to threefold increase in Km for arginine, the same replacement in Scapharca AK had no pronounced effect on enzyme activity. Together with the observation that bivalve AKs are phylogenetically distinct from other molluskan AKs, these results suggest that bivalve AKs have undergone a unique molecular evolution; the characteristic stabilizing function of residues 62 and 193 has been lost and, consequently, the enzyme shows higher activity than normal.Received 14 October 2003; accepted 1 November 2003 相似文献