Cytoglobin ligand binding regulated by changing haem-co-ordination in response to intramolecular disulfide bond formation and lipid interaction

2014 ◽  
Vol 465 (1) ◽  
pp. 127-137 ◽  
Author(s):  
Penny Beckerson ◽  
Michael T. Wilson ◽  
Dimitri A. Svistunenko ◽  
Brandon J. Reeder
Keyword(s):  
Ligand Binding ◽  
Redox State ◽  
Structural Changes ◽  
Bond Formation ◽  
Lipid Binding ◽  
Binding Kinetics ◽  
Disulfide Bond Formation ◽  
Physiological Properties ◽  
Intramolecular Disulfide Bond ◽  
Lipid Interaction

The redox state of the two-surface exposed cysteine residues in cytoglobin (Cygb) regulates the biochemical and potential physiological properties of the protein. Significant changes to ligand-binding kinetics, peroxidase activity and lipid-binding-induced structural changes are observed.

scholarly journals Disulfide Bond Formation in Secreton Component PulK Provides a Possible Explanation for the Role of DsbA in Pullulanase Secretion

2001 ◽  
Vol 183 (4) ◽  
pp. 1312-1319 ◽  
Author(s):  
Anthony P. Pugsley ◽  
Nicolas Bayan ◽  
Nathalie Sauvonnet
Keyword(s):  
Disulfide Bond ◽  
Klebsiella Oxytoca ◽  
Bond Formation ◽  
Type Ii Secretion ◽  
Disulfide Bond Formation ◽  
Gene Encoding ◽  
Intramolecular Disulfide Bond ◽  
Disulfide Oxidoreductase ◽  
Considerable Excess

ABSTRACT When expressed in Escherichia coli, the 15Klebsiella oxytoca pul genes that encode the so-called Pul secreton or type II secretion machinery promote pullulanase secretion and the assembly of one of the secreton components, PulG, into pili. Besides these pul genes, efficient pullulanase secretion also requires the host dsbA gene, encoding a periplasmic disulfide oxidoreductase, independently of disulfide bond formation in pullulanase itself. Two secreton components, the secretin pilot protein PulS and the minor pseudopilin PulK, were each shown to posses an intramolecular disulfide bond whose formation was catalyzed by DsbA. PulS was apparently destabilized by the absence of its disulfide bond, whereas PulK stability was not dramatically affected either by adsbA mutation or by the removal of one of its cysteines. The pullulanase secretion defect in a dsbA mutant was rectified by overproduction of PulK, indicating reduced disulfide bond formation in PulK as the major cause of the secretion defect under the conditions tested (in which PulS is probably present in considerable excess of requirements). PulG pilus formation was independent of DsbA, probably because PulK is not needed for piliation.

scholarly journals Cardiac peroxiredoxins undergo complex modifications during cardiac oxidant stress

2008 ◽  
Vol 295 (1) ◽  
pp. H425-H433 ◽  
Author(s):  
Ewald Schröder ◽  
Jonathan P. Brennan ◽  
Philip Eaton
Keyword(s):  
Hydrogen Peroxide ◽  
Disulfide Bond ◽  
Disulfide Bonds ◽  
Structural Changes ◽  
Oxidant Stress ◽  
Bond Formation ◽  
Redox Signaling ◽  
Size Exclusion ◽  
Disulfide Bond Formation ◽  
Dimeric Unit

Peroxiredoxins (Prdxs), a family of antioxidant and redox-signaling proteins, are plentiful within the heart; however, their cardiac functions are poorly understood. These studies were designed to characterize the complex changes in Prdxs induced by oxidant stress in rat myocardium. Hydrogen peroxide, a Prdx substrate, was used as the model oxidant pertinent to redox signaling during health and to injury at higher concentrations. Rat hearts were aerobically perfused with a broad concentration range of hydrogen peroxide by the Langendorff method, homogenized, and analyzed by immunoblotting. Heart extracts were also analyzed by size-exclusion chromatography under nondenaturing conditions. Hydrogen peroxide-induced changes in disulfide bond formation, nonreversible oxidation of cysteine (hyperoxidation), and subcellular localization were determined. Hydrogen peroxide induced an array of changes in the myocardium, including formation of disulfide bonds that were intermolecular for Prdx1, Prdx2, and Prdx3 but intramolecular within Prdx5. For Prdx1, Prdx2, and Prdx5, disulfide bond formation can be approximated to an EC50 of 10–100, 1–10, and 100–1,000 μM peroxide, respectively. Hydrogen peroxide induced hyperoxidation, not just within monomeric Prdx (by SDS-PAGE), but also within Prdx disulfide dimers, and reflects a flexibility within the dimeric unit. Prdx oxidation was also associated with movement from the cytosolic to the membrane and myofilament-enriched fractions. In summary, Prdxs undergo a complex series of redox-dependent structural changes in the heart in response to oxidant challenge with its substrate hydrogen peroxide.

Inhibition of Human Cytomegalovirus UL80 Protease by Specific Intramolecular Disulfide Bond Formation†

Biochemistry ◽  
1996 ◽  
Vol 35 (18) ◽  
pp. 5838-5846 ◽  
Author(s):  
Ellen Z. Baum ◽  
Marshall M. Siegel ◽  
Geraldine A. Bebernitz ◽  
Jeffrey D. Hulmes ◽  
Latha Sridharan ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Intramolecular Disulfide Bond

Charcoal surface-assisted catalysis of intramolecular disulfide bond formation in peptides

2009 ◽  
Vol 51 (5) ◽  
pp. 365-369 ◽  
Author(s):  
RUDOLF VOLKMER-ENGERT ◽  
CHRISTIANE LANDGRAF ◽  
JENS SCHNEIDER-MERGENER
Keyword(s):  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Intramolecular Disulfide Bond

Control of the toxic conformation of amyloid β42 by intramolecular disulfide bond formation

2020 ◽  
Vol 56 (29) ◽  
pp. 4118-4121 ◽  
Author(s):  
Yuka Matsushima ◽  
Ryo C. Yanagita ◽  
Kazuhiro Irie
Keyword(s):  
Amino Acid ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Amino Acid Residues ◽  
Intramolecular Disulfide Bond

An Aβ42 analog crosslinked within the molecule at the 17th and 28th amino acid residues exhibited high aggregative ability and potent neurotoxicity comparable to those of E22P-Aβ42.

scholarly journals Role of the Intramolecular Disulfide Bond in FlgI, the Flagellar P-Ring Component of Escherichia coli

2006 ◽  
Vol 188 (12) ◽  
pp. 4190-4197 ◽  
Author(s):  
Yohei Hizukuri ◽  
Toshiharu Yakushi ◽  
Ikuro Kawagishi ◽  
Michio Homma
Keyword(s):  
Escherichia Coli ◽  
Disulfide Bond ◽  
Self Assembly ◽  
Bacterial Species ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Wild Type ◽  
Ring Assembly ◽  
Intramolecular Disulfide Bond

ABSTRACT The P ring of the bacterial flagellar motor consists of multiple copies of FlgI, a periplasmic protein. The intramolecular disulfide bond in FlgI has previously been reported to be essential for P-ring assembly in Escherichia coli, because the P ring was not assembled in a dsbB strain that was defective for disulfide bond formation in periplasmic proteins. We, however, found that the two Cys residues of FlgI are not conserved in other bacterial species. We then assessed the role of this intramolecular disulfide bond in FlgI. A Cys-eliminated FlgI derivative formed a P ring that complemented the flagellation defect of our ΔflgI strain when it was overproduced, suggesting that disulfide bond formation in FlgI is not absolutely required for P-ring assembly. The levels of the mature forms of the FlgI derivatives were significantly lower than that of wild-type FlgI, although the precursor protein levels were unchanged. Moreover, the FlgI derivatives were more susceptible to degradation than wild-type FlgI. Overproduction of FlgI suppressed the motility defect of ΔdsbB cells. Additionally, the low level of FlgI observed in the ΔdsbB strain increased in the presence of l-cystine, an oxidative agent. We propose that intramolecular disulfide bond formation facilitates the rapid folding of the FlgI monomer to protect against degradation in the periplasmic space, thereby allowing its efficient self-assembly into the P ring.

Pressure Effects on the Ligand-Binding Kinetics for Hemoproteins and Their Site-Directed Mutants

1996 ◽  
Author(s):  
Isao Morishima
Keyword(s):  
High Pressure ◽  
Amino Acid ◽  
Ligand Binding ◽  
Pressure Dependence ◽  
Activation Volume ◽  
Bond Formation ◽  
Binding Kinetics ◽  
Amino Acid Residues ◽  
Association Reaction ◽  
Human Myoglobin

The effects of high pressure up to 1500 bar on the recombination kinetics of oxygen and carbon monoxide (CO) binding to human hemoglobin (intact and isolated chain forms), human myoglobin (and its mutants), and cytochrome P-450 were studied by the use of millisecond and nanosecond laser photolysis. The activation volumes for the binding of CO to the R- and T-quaternary states of hemoglobin (Hbs) were determined to be –9.0 and –31.7 ml, respectively. The characteristic pressure dependence of the activation volume was observed for the R-state Hb but not for the T-state Hb. More detailed studies were made with isolated α- and β-chains of human Hb. The kinetic data were analyzed on the basis of a simple three-species model, which assumes two elementary reaction processes of bond formation and steps of ligand migration. A pressure-dependent activation volume change from negative lo positive values in the bimolecular CO association reaction was observed for both chains. This is attributed to a change of the rate-limiting step from the bond-formation step to the ligandmigration step. High-pressure ligand-binding kinetics were also examined for site-specific mutants of human myoglobin in which some amino acid residues at the heme distal sites, such as Leu 29, Lys 45, Ala 66, and Thr 67, are substituted by others. The pressure dependence of the CO binding rate for the L29 mutants was unusual: a positive value was obtained unexpectedly for overall CO binding. Corresponding to this anomaly was an unusual geometry of the iron-bound CO, which was determined by IR and NMR spectroscopies. The effects of camphor and camphor analogues as substrates on the CO-binding kinetics for P-450cam were also studied under pressure. The positive activation volumes for CO binding were obtained for substrate-free and norcamphor- and adamantane-bound P-450, whereas other substrate analogue-bound P-450 complexes exhibited the negative activation volumes. All of the present high-pressure results are discussed in relation to (1) the dynamic aspects of the protein conformation, and (2) the specific participation of amino acid residues in the heme distal site in each elementary step of the ligand-binding reaction process.

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