Antioxid Redox Signal 14, —, doi: Cook, K. Post-translational control of protein function by disulfide bond cleavage. Antioxid Redox Signal 18, —, doi: Hogg, P. Disulfide bonds as switches for protein function. Trends Biochem Sci 28, — Schmidt, B. Allosteric disulfide bonds.
Biochemistry 45, —, doi: Humphries, K. Aging: a shift from redox regulation to oxidative damage. Free Radic Res 40, —, doi: Halliwell, B. Pierce, G. Inflammation in nonhealing diabetic wounds: the space-time continuum does matter. Am J Pathol , —, doi: Babior, B. Phagocytes and oxidative stress. Am J Med , 33—44 Alderton, W. Nitric oxide synthases: structure, function and inhibition. Biochem J , — Radi, R.
Unraveling peroxynitrite formation in biological systems. Free Radic Biol Med 30, — Klebanoff, S. Myeloperoxidase: a front-line defender against phagocytosed microorganisms. J Leukocyte Biol 93, —, doi: Davies, M. Mammalian heme peroxidases: from molecular mechanisms to health implications. Antioxid Redox Signal 10, —, doi: Winterbourn, C. Reactive oxygen species and neutrophil function. Ann Rev Biochem 85, —, doi: Myeloperoxidase-derived oxidation: mechanisms of biological damage and its prevention.
J Clin Biochem Nutr 48, 8—19, doi: The oxidative environment and protein damage. Biochim Biophys Acta , 93— Protein oxidation and peroxidation.
Schoneich, C. Thiyl radicals and induction of protein degradation. Free Radic Res 50, — Trujillo, M. One- and two-electron oxidation of thiols: mechanisms, kinetics and biological fates. Torosantucci, R. Oxidation of therapeutic proteins and peptides: structural and biological consequences. Pharm Res 31, —, doi: Jiskoot, W. Protein instability and immunogenicity: roadblocks to clinical application of injectable protein delivery systems for sustained release.
J Pharm Sci , —, doi: Livney, Y. Specificity of disulfide bond formation during thermal aggregation in solutions of beta-lactoglobulin B and kappa-casein A. J Agric Food Chem 52, —, doi: Kurouski, D. The impact of protein disulfide bonds on the amyloid fibril morphology. Int J Biomed Nanosci Nanotechnol 2, —, doi: Takase, K.
Aggregate formation and the structure of the aggregates of disulfide-reduced proteins. J Protein Chem 21, — Chattopadhyay, M. The disulfide bond, but not zinc or dimerization, controls initiation and seeded growth in amyotrophic lateral sclerosis-linked Cu,Zn superoxide dismutase SOD1 fibrillation. J Biol Chem , —, doi: Solsona, C.
Altered thiol chemistry in human amyotrophic lateral sclerosis-linked mutants of superoxide dismutase 1. Storkey, C. Reevaluation of the rate constants for the reaction of hypochlorous acid HOCl with cysteine, methionine, and peptide derivatives using a new competition kinetic approach.
Free Radic Biol Med 73, 60—66, doi: Szarek, W. Anomeric effect, origin and consequence. Kirby, A. The anomeric effect and related stereoelectronic effects at oxygen eds K. Hafner et al. Thatcher, G.
The anomeric effect and associated stereoelectronic effects. Weinhold, F. Vager — Ferrer-Sueta, G. Factors affecting protein thiol reactivity and specificity in peroxide reduction. Chem Res Toxicol 24, —, doi: Hawthorne and K. Vandenbroeck , Anal. Martens , I. Alloza , C. Scott , A.
Billiau and K. Vandenbroeck , Eur. Marquardt , D. Hebert and A. Hebert , B. Foellmer and A. Hebert , J. Zhang , W. Chen , B. Solda , N. Garbi , G. Hammerling and M. Molinari , J. Chiu , N. Venkatesan , C.
Chou , H. Chen , S. Lian , S. Liu , C. Huang , W. Lian , P. Chong and C. Leng , Biochem. Daly , J. Djordjevic , P. Kroon and R. Fass , S. Blacklow , P. Kim and J. Gent and I. Braakman , Cell. Life Sci. Jansens , E. Jorgensen , O. Jensen , H. Holst , J. Hansen , T. Corydon , P. Bross , L. Bolund and N. Gregersen , J. Oka , M. Pringle , I. Schopp , I. Braakman and N. Bulleid , Mol. Cell , , 50 , — CrossRef PubMed. Lehrman , W. Schneider , T. Sudhof , M.
Brown , J. Goldstein and D. Blacklow and P. Kim , Nat. Cemazar , S. Zahariev , J. Lopez , O. Carugo , J. Jones , P. Hore and S. Pongor , Proc. Chng , M. Xue , R.
Garner , H. Kadokura , D. Boyd , J. Beckwith and D. Vitkup , C. Sander and G. Church , Genome Biol. Fra , E. Yoboue and R.
Sitia , Front. Behnke , M. Feige and L. Tannous , G. Pisoni , D. Hebert and M. Molinari , Semin. Cell Dev. Lanzi , S. Ferrari , M. Vihinen , S. Caraffi , N. Kutukculer , L. Schiaffonati , A. Plebani , L. Notarangelo , A. Fra and S. Patel , K. Bartoli , R. Fandino , A. Ngatchou , G. Woch , J. Carey and J. Tanaka , Invest. Visual Sci. Bernascone , S. Vavassori , A. Di Pentima , S. Santambrogio , G. Lamorte , A. Amoroso , F.
Scolari , G. Ghiggeri , G. Casari , R. Polishchuk and L. Wang , D. Groeneveld , G. Cosemans , R. Dirven , K. Valentijn , J. Voorberg , P. Reitsma and J. Mitsuhashi , H. Mitsuhashi , M. Alexander , H. Sugimoto and P. Sun , C. Liu , R. Wang , C. Paddock and P. Asai , T. Iwashita , M. Matsuyama and M. Takahashi , Mol.
Kjaer and C. Ibanez , Hum. Mulligan , J. Kwok , C. Healey , M. Elsdon , C. Eng , E. Gardner , D. Love , S. Mole , J. Moore and L. Papi , et al. Santoro , F. Carlomagno , A. Romano , D. Bottaro , N. Dathan , M. Grieco , A. Fusco , G. Vecchio , B. Matoskova and M. Kraus , et al. Cosma , M. Cardone , F. Carlomagno and V. Colantuoni , Mol. Lobito , F. Kimberley , J. Muppidi , H. Komarow , A. Jackson , K. Hull , D. Kastner , G.
Screaton and R. Hobbs , M. Russell , J. Lelli , R. Garuti , P. Pedrazzi , M. Ghisellini , M. Simone , R. Tiozzo , L. Cattin , M. Valenti , M. Rolleri and S. Bertolini , et al. Maksemous , R. Smith , L. Haupt and L. Griffiths , Hum. Genomics , , 10 , 38 CrossRef PubMed.
Meng , X. Zhang , G. Lee , Y. Chen , I. Prudovsky and M. Almeida , L. Zhou and F. Kleinberger , A. Capell , N. Brouwers , K. Fellerer , K. Sleegers , M. Cruts , C. Van Broeckhoven and C. Haass , Neurobiol. Aging , , 39 , e — e CrossRef PubMed.
Wang , P. Van Damme , C. Cruchaga , M. Gitcho , J. Vidal , M. Seijo-Martinez , L. Wang , J. Robberecht and A. Goate , J. Shankaran , A. Capell , A. Hruscha , K. Fellerer , M. Neumann , B. Schmid and C. Haass , J. Stoy , E. Edghill , S. Flanagan , H. Paz , A. Pluzhnikov , J. Below , M. Hayes , N. Cox , G. Lipkind , R. Lipton , S. Greeley , A. Patch , S. Ellard , D. Steiner , A. Hattersley , L. Philipson , G. Bell and G. Neonatal Diabetes International Collaborative , Proc.
Cunningham , N. Manickam , M. Liu , P. Arvan and B. Tsai , Mol. Cell , , 26 , — CrossRef PubMed. Liu , L. Haataja , J. Wright , N. Wickramasinghe , Q. Hua , N. Phillips , F. Barbetti , M. Weiss and P. Ikonen , N. Enomaa , I. Ulmanen and L. Itoh , M. NMR also allows to analyze structural and dynamic aspects of transient oxidative folding processes Szekely et al.
In the following sections, we present a short overview of NMR applications for the characterization of disulfide-bond containing biomolecules. To emphasize the special role of cysteines as a structure-forming or catalytic unit in the context of an evolutionary process, we present a short analysis of proteomes from different domains of life. Questions that arise are: I how many proteins of a proteome contain cysteines, II what is the average number of cysteines and disulfide bonds in a protein, III are there differences in the protein length or overall amino acid distribution among proteins with and without cysteines, and IV does the occurrence of cysteines correlate with the accumulation of other amino acids or amino acid patterns around these cysteines?
In a first step, we selected different representatives from the three domains of life Archaea: T. Except for T. Proteins in the data set are either annotated as reviewed manually annotated or unreviewed full manual annotation still pending. Besides, we examined a data set that comprises all reviewed records in UniProt referred herein as Reviewed SwissProt. Eighty-three percent of all proteins annotated as reviewed in UniProt contain at least one cysteine and the number of cysteines accounts for 1.
Table 1 , Figure S3. The median length of coding sequences of proteins for all reviewed entries in UniProt is a. The cysteine-containing proteins are, on average, significantly longer a. On average 3 cysteines are present in proteins included in the SwissProt data set and 4 cysteines if only cysteine-containing proteins are considered.
It is well-known that the median protein length in Eukaryotes is significantly longer than in Prokaryotes. Among Prokaryotes, Bacteria tend to have longer proteins, on average, than Archaea Zhang, ; Skovgaard et al.
Concerning the median protein length, the trends presented in Table 1 confirm the results observed by others Zhang, ; Skovgaard et al. With only a median protein length of a. The genomic protein length distribution for each selected species is given in detail in Figure S5. Figures S7 , S8 depict the genomic length distribution of cysteine-containing proteins and proteins without cysteines, respectively.
The protein abundance database [PAXdb, Wang et al. With the exceptions of T. Intriguingly, the abundance weighted median number of cysteines per protein is 4 to 5 in all selected eukaryotes and is lower than on the genetic level. The frequency of cysteines seems to increase during evolution.
While in T. This observation is also reflected in the species-specific cysteine percentage proportion of all amino acids 0. Moreover, the median number of cysteines per protein tends to increase during evolution and reaches with 9 cysteines per protein in humans a maximum.
For a detailed analysis of the genomic and abundance weighted cysteine distribution see Figures S9 , S10 , respectively. In the reviewed SwissProt data set the SCO-spondin proteins contain the highest number of cysteins [e. It has to be noted that among the selected organisms the reference proteome of D. If the difference in the amino acid distribution of non-cysteine-containing proteins compared to cysteine-containing proteins is considered Figure S4 , it is notable that, except for T.
It is still subject to speculation if the structural or functional role of cysteines is compensated by an increase of, e. In Figures S1 , S2 we present the position-dependent amino acid frequency in cysteine-containing proteins. In each protein, which carries a cysteine, the amino acid distribution at each position N- and C-terminal stepwise next to cysteine is determined and compared to the overall amino acid distribution.
It becomes clear that besides cysteine, mainly aromatic amino acids are more frequent around cysteines in all selected data sets. Particularly in the H. These findings may reflect the widespread zinc finger structural motif. They are mostly found in secretory proteins and extracellular domains of membrane proteins.
Table 1 and Figures S11, S12 compile some statistical information about reviewed proteins with disulfide bonds. As already mentioned above, for the content of cysteines, the conotoxins e. For the selected data sets, the content of proteins with at least one intra-chain disulfide bond increase during evolution Table 1. Eighteen percent of all reviewed human proteins bear at least one disulfide bond.
However, as this protein contains cysteines, it immediately becomes clear that not all of them under the same physical conditions form intramolecular disulfide pairs. In contrast, in T. The observation that the cysteine content in proteins increases during evolution can't be transferred clearly to the median number of disulfide bonds.
The chirality of the disulfide linkage is a stereo-electronic consequence of the four free electron pairs on the two sulfur atoms. Armstrong et al. Figure 1. Distribution values which are outside 10 times the standard deviation were removed from each correlation data set. Contour levels reflect the total number of correlations within. This empirical analysis was later supported by results of quantum chemical calculations of cysteine chemical shifts Martin et al. As introduced above, disulfide bridges favor two distinct chiralities.
In addition to a pure NOE-based NMR structure determination, the measurement of residual dipolar couplings RDC allows to improve the resolution of 3D structures in case isotopically labeled compounds are available. Lately, combining seleno-cysteine scanning and NMR analysis was shown to be a reliable approach for mapping disulfide bonds in cysteine-rich peptides and proteins Denisov et al. The structurally conservative selenium substitution causes selective chemical shift changes of cysteine carbons involved in the mixed S—Se bond allowing identification by visual comparison of [ 1 H, 13 C]-HSQC spectra of native and Sec-mutants.
Conotoxins, small disulfide bridge-containing peptides found in marine cone snails, have attracted considerable scientific interest as they bind to ion channels. The pharmacological potential to modulate or block the ion channel activity and their synthetic availability make conotoxins promising candidates for new analgesics.
However, Heimer et al. With respect to this, ionic liquids have proven to be a promising solvent for controlling the oxidative folding process Miloslavina et al. The data supports the notion that the two disulfide bonds have been selectively conserved to create and stabilize a structural scaffold optimized for receptor binding.
Two recent publications presented structural relatedness between conotoxin structures and the granulin module, which was also solved by NMR and typically contains six disulfide bridges Hrabal et al. Also for the conotoxin N ext H-Vc7. Based on further occurrences of this motif, e. From earlier studies it is known that protease inhibitors, e.
Kunitz-type proteins, with bovine basic pancreatic trypsin inhibitor BPTI as the most extensively studied member Berndt et al. Recently, Banijamali et al. Also, Ixolaris, a potent tick salivary anticoagulant binding the coagulation factor Xa and the zymogen FX, shows a canonical Kunitz 3D structure De Paula et al. However, the NMR and modeling results indicate that it exhibits a non-canonical inhibition interaction outside the active site of FX. These structural features can induce a stable, compact core and an extended binding loop.
This reduction of disulfide bonds can be accomplished by treatment with 2-Mercaptoethanol. Disulfide bonds play an important protective role for bacteria as a reversible switch that turns a protein on or off when bacterial cells are exposed to oxidation reactions. Hydrogen peroxide H 2 O 2 in particular could severely damage DNA and kill the bacterium at low concentrations if not for the protective action of the SS-bond.
Disulfide bonds also play a significant role in the vulcanization of rubber. In eukaryotic cells, disulfide bonds are generally formed in the lumen of the RER rough endoplasmic reticulum but not in the cytosol. This is due to the oxidative environment of the ER and the reducing environment of the cytosol see glutathione. Thus disulfide bonds are mostly found in secretory proteins, lysosomal proteins, and the exoplasmic domains of membrane proteins.
There are notable exceptions to this rule. A number of cytosolic proteins have cysteine residues in proximity to each other that function as oxidation sensors; when the reductive potential of the cell fails, they oxidize and trigger cellular response mechanisms. Vaccinia virus also produces cytosolic proteins and peptides that have many disulfide bonds; although the reason for this is unknown presumably they have protective effects against intracellular proteolysis machinery.
Disulfide bonds are also formed within and between protamines in the sperm chromatin of many mammalian species. Hair proteins are held together by disulfide bonds, from the amino acid cysteine.
These links are very robust: for example, virtually intact hair has been recovered from ancient Egyptian tombs, and the disulfide links also cause hair and feathers which have similar keratins to be extremely resistant to protein digestive enzymes. Different parts of the hair and feather have different cysteine levels, leading to harder or softer material. Breaking and making disulfide bonds governs the phenomenon of wavy or frizzy hair.
It is breaking and remaking of the disulfide bonds which is the basis for the permanent wave in hairstyling. In feathers , the high disulfide content dictates the high sulfur content of bird eggs, which need to contain enough sulfur to feather the chick. In both hair and feathers, the high sulfur content due to the high number of disulfides causes the disagreeable smell of the material when it is burned.
Categories: Protein structure Posttranslational modification. Read what you need to know about our industry portal bionity.
0コメント