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S G Mayhew

Publications and source records attributed to S G Mayhew.

At least 73 records · Page 4Linked to original sources

Properties of the hydrogenase of Megasphaera elsdenii.

The catalytic activities of Megasphaera elsdenii hydrogenase are stimulated by salts. The stimulation is due to the anion: the more chaotropic the anion, the greater the effect. Dithionite-reduced and dye-oxidised preparations of hydrogenase are inactivated by reaction with oxygen. The inactivation of the reduced enzyme by excess oxygen follows pseudo-first-order kinetics; the reaction order for the oxidised enzyme has not been established. The rate of oxygen-inactivation is decreased by bovine serum albumin. The hydrogen production activity decreases in the presence of dimethylsulphoxide and ethylene glycol. The hydrogen oxidation activity is stimulated by dimethylsulphoxide, and the activity remains linear with time at concentrations up to 50% (v/v). Above 70% dimethylsulphoxide the steady-state activity of hydrogenase is abolished for both types of activity. The enzyme is more stable in a hydrogen atmosphere than in an argon atmosphere, and the oxidized enzyme is more stable than the reduced enzyme. The enzyme is isolated in the presence of dithionite and it is therefore reduced. When the enzyme is oxidized by treatment with 2,6-dichloroindophenol or with (bi)sulphite, its activity increases by up to 65%; this activation is not reversed when the enzyme is re-reduced. The increase in activity is associated with a change of the redox potential of the incubation medium to a less negative value; half of the maximum activation occurs at -0.41 V. The electron paramagnetic resonance spectrum of the dithionite-reduced hydrogenase resembles that of a reduced ferredoxin-type of spectrum with two 4Fe-4S clusters. The spectrum of the oxidized enzyme is similar to that of Chromatium high-potential iron-sulphur protein. No redox potentials can be ascribed to these spectra since the redox system changes upon freezing to liquid helium temperatures.

Aerobiosis↗

Purification and properties of hydrogenase from Megasphaera elsdenii.

A hydrogenase has been purified to homogeneity from the soluble fraction of the rumen bacterium Megasphaera elsdenii, the overall purification is 200 times with a yield of 14%. The pure enzyme consists of a single polypeptide chain with Mr approximately 50 000 which contains 12 atoms of non-haem iron and 12 atoms of acid-labile sulphide. The enzyme is rapidly inactivated by O2 and it is therefore purified under nitrogen and in the presence of sodium dithionite. The optical spectrum of the enzyme, after removal of the dithionite with air, shows a peak at 275 nm (epsilon 275 nm = 143 mM-1 cm-1) and a shoulder between 350 nm and 400 nm (epsilon 400 nm = 46 mM-1 cm-1). The enzyme catalyses hydrogen production from sodium dithionite at a low rate. The rate is greatly enhanced by addition of the electron donors flavodoxin, ferredoxin and methyl viologen. The kinetic data with these three electron donors suggest co-operativity, but no indication of self-association of the enzyme was obtained. Sodium chloride enhances the rate of hydrogen production with methyl viologen semiquinone and changes the kinetic behaviour of the enzyme with this electron donor, but causes inhibition of the reactions mediated by ferredoxin and flavodoxin. Two kinetic models were developed which are consistent with the kinetic data of the three electron donors tested. The apparent co-operativity for the hydrogen production can be fitted with the mathematical form of those models. The identical kinetic behaviour of the hydrogenase with the one-electron donors flavodoxin and methyl viologen semiquinone monomer and the two-electron donor ferredoxin indicates that the hydrogenase accepts two electrons in two separate, independent steps and further indicates that the two (4Fe-4S) clusters of the donor ferredoxin are independent. The interpretation of the kinetic data with methyl viologen semiquinone is complicated by the fact that the semiquinone dimerises, and that the formation of the dimer is enhanced by salt. Taking into account the association of this donor, the activity of the enzyme with methyl viologen semiquinone can be described by the sum of the activities of the enzyme with methyl viologen monomer and methyl viologen dimer. The enzyme catalyses the oxidation of hydrogen gas with methyl and benzyl viologen as electron acceptors to their semiquinone forms; both electron acceptors show Michaelis-Menten kinetics. The hydrogen oxidation activity with both electron acceptors is stimulated by addition of sodium chloride. The kinetic data of the oxidation of hydrogen with the two-electron acceptors used are consistent with the porposed models, if it is assumed that the pathway followed is compulsory. At this moment no choice can be made between the models proposed.

Computers↗

The redox potential of dithionite and SO-2 from equilibrium reactions with flavodoxins, methyl viologen and hydrogen plus hydrogenase.

1. It has been shown that redox equilibria can be formed between dithionite ion (plus SO-2) and (bi)sulphite, and the low-potential electron carriers flavodoxin and methyl viologen. The equilibria were established either by treating the oxidized electron carriers with dithionite, or by treating flavodoxin hydroquinone or methyl viologen semiquinone with (bi)sulphite. Similar redox equilibria were established between dithionite/(bi)sulphite and hydrogen using catalytic amounts of hydrogenase in the presence of a low-potential electron carrier. The effects of pH and temperature on the equilibria were determined. 2. The equilibria were analyzed to determine the redox potential of the dithionite/(bi)sulphite system. In accordance with the results of earlier kinetic studies, it was assumed that the reductant in dithionite solutions is the dissociation product SO-2. The calculated midpoint redox potential E' for the couple SO-2/HSO-3 at pH 7 and 25 degrees C was -0.66 V. The reductant is present largely as the dimer at concentrations of dithionite above about 10nM. Consequently, the midpoint potential, Em, of dithionite solutions becomes less negative as the concentration of dithionite is increased (deltaEm/deltalog S2O2-4 = 29 mV). The theoretical potential of a solution of 1 M S2O2-4 and 2 M (bi)sulphite at pH 7 was calculated to be -0.386V. This value is 59 mV more negative than that determined in 1911 by potentiometry, but considerably more positive than other values in the literature. The effects of pH on the equilibria showed that E' is controlled by the pK of (bi)sulphite at 6.9; the slope deltaE'/deltapH was -59 mV below the pK and -118 mV above the pK. The effects of temperature on the equilibria suggested that Em for dithionite changed by -1.6 mV/degrees C for a rise in temperature between 2 degrees C and 40 degrees C. If sodium dithionite is contaminated with small amounts of (bi)sulphite, its addition in large excess to a low potential electron carrier can cause oxidation of the carrier.

Anaerobiosis↗

A continuous fluorometric assay for flavokinase. Properties of flavokinase from Peptostreptococcus elsdenii.

A continuous fluorometric assay that utilizes apoflavodoxin as a trapping agent for riboflavin 5'-phosphate (FMN) has been developed for flavokinase (ATP:riboflavin 5'-phosphotransferase, EC 2.7.1.26). Use of this assay is illustrated in a procedure for the partial purification of flavokinase from the strict anaerobe Peptostreptococcus elsdenii. The purified enzyme catalyzed the formation of 8.3 nmol FMN - min-1 - mg-1 at 37 degrees C and had apparent Km values for riboflavin and ATP of 10 and 4.7 micronM, respectively. ATP could be replaced by ADP (22% of the rate observed with ATP) but not by GTP. The enzyme also phosphorylated 5-deaza- and 8-bromoriboflavin with activities of 15 and 70%, respectively, of that with riboflavin; it was inactive with iso riboflavin and deoxyriboflavin.

Kinetics↗

Studies on the binding of FMN by apoflavodoxin from Peptostreptococcus elsdenii, pH and NaCl concentration dependence.

1. The pH and ionic strength dependence of the interaction of FMN with apoflavodoxin has been studied by fluorometry in the pH region 2-5, at 22 degrees C. 2. The rate constant of dissociation and the dissociation constant were experimentally determined; the rate constants of association were claculated at a given pH value. These constants depend on the ionic strength. The plots of these constants against the square root of the ionic strength are straight. 3. Our data have been interpreted in terms of the Brönsted theory, which relates chemical reaction rates to ionic strength. The data indicate that the apoenzyme reaches its maximum net positive charge at pH 2.0-2.6. The calculated net charge in this pH region is between 11 and 12 and is in agreement with the theoretical value of 12 as deduced from the primary structure of the protein. The isoelectric point of the holoenzyme is about 4. 4. The rate constant of association extrapolated to zero ionic strength is 3.2-10(5)M-1-s-1 and is pH-independent. 5. The rate constant of dissociation and the dissociation constant extrapolated to zero ionic strength depend on the pH. The results are explained by assuming that there are two protein ionizations with a pK value of 3.4; these ionizing groups are possibly close to the FMN binding site.

Apoproteins↗

Identification and properties of 8-hydroxyflavin--adenine dinucleotide in electron-transferring flavoprotein from Peptostreptococcus elsdenii.

1. A new flavin prosthetic group has been isolated in pure form from the electron-transferring flavoprotein of Peptostreptococcus elsdenni. Its structure has been established as the FAD derivative of 7-methyl-8-hydroxyisoalloxazine: (see article). Proof of this structure has been obtained by chemical syntehsis of 7-methyl-8-hydroxyisoalloxazine models, and by stepwise degradation of the native compound to 7-methy-8-hydroxyalloxazine. The orange chromophore is characterized by a strong absorption band with a maximum at 472 nm (xi = 41 000 M-1 CM-1) and a pK at 4.8 due to the ionisation of the C(8)-OH group. 2. The properties of a series of functionally substituted derivatives of 8-hydroxy flavins and lumichromes have been investigated to provide a basis for interpreting the effects of pH on the spectroscopic properties of the 8-hydroxy derivatives of FAD and FMN. 3. The 8-hydroxy derivative of FAD is bound by apo-D-amino acid oxidase; the complex shows no catalytic activity. The 8-hydroxy derivative of FMN is bound by apoflavodoxin to give a complex which has catalytic activity similar to that of native flavodoxin. The complex is reversibly reduced by dithionite, first to a relatively stable semiquinone and further to the dihydroflavin form.

Binding Sites↗

Properties of immobilized flavodoxin from Peptostreptococcus elsdenii. An affinity ligand for the purification of riboflavin 5'-phosphate (FMN) and its analogues.

The small flavoprotein, flavodoxin, isolated from Peptostreptococcus elsdenii, has been covalently coupled to CNBr-activated Sepharose 4B. The immobilized protein replaces ferredoxin as an electron carrier in hydrogen production from dithionite or pyruvate in the presence of ferredoxin-free extracts of P. elsdenii; compared with soluble flavodoxin, its activities in these systems are 13% and 3.5% respectively. Acid treatment reversibly dissociates FMN from the immobilized protein. The dissociation constant of the complex with FMN, determined by fluorimetric titration, is 1.5 (+/- 0.4) nM, and is therefore very little different from that of soluble flavodoxin. Like soluble apoflavodoxin, the immobilized apoprotein is highly specific for flavins with an N-10 side-chain of 5 carbon atoms and a C-5' phosphate group. Approximately half of the flavin impurity in commercial preparations of FMN (12-15% of the total flavin), and similar impurity in synthetic analogues of FMN, is not separated by conventional purification procedures, but it is readily and conveniently removed by affinity chromatography with apoflavodoxin as the immobilized ligand. The immobilized protein is stable for long periods; its capacity for FMN decreases by only 20% after 15 cycles of flavin dissociation and reassociation during several months.

Bacterial Proteins↗