Succinate: quinone oxidoreductases: new insights from X-ray crystal structures

Lancaster, C. Roy D.; Kröger, Achim

doi:10.1016/s0005-2728(00)00180-8

Cited by 63 publications

(38 citation statements)

References 43 publications

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“…The global effects of the PAL mutations in cyt b 561 are reminiscent of results with the cytochrome b subunit of quinol:fumarate reductase from Wolinella succinogenes, where mutation of any of the four histidines predicted to be axial ligands to the hemes (69) resulted in little or no expression of the protein (70). Assignment of those histidines as axial ligands was later confirmed by crystallography (71).…”

Section: Identification Of Axial Ligands For Cyt B 561 Hemesmentioning

confidence: 91%

Axial Ligation and Stoichiometry of Heme Centers in Adrenal Cytochromeb₅₆₁

Kamensky

Tsai

et al. 2007

Biochemistry

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Cytochrome (cyt) b 561 transports electrons across the membrane of chromaffin granules (CG) present in the adrenal medulla, supporting the biosynthesis of norepinephrine in the CG matrix. We have conducted a detailed characterization of cyt b 561 using electron paramagnetic resonance (EPR) and optical spectroscopy on the wild type and mutant forms of the cytochrome expressed in insect cells. The g z = 3.7 (low-potential heme) and g z = 3.1 (high-potential heme) signals were found to represent the only two authentic hemes of cyt b 561 ; models that propose smaller or greater amounts of heme can be ruled out. We identified the axial ligands to hemes in cyt b 561 by mutating four conserved histidines (His54 and His122 at the matrix-side heme center and His88 and His161 at the cytoplasmicside heme center), thus confirming earlier structural models. Single mutations of any of these histidines produced a constellation of spectroscopic changes that involve not one but both heme centers. We hypothesize that the two hemes and their axial ligands in cyt b 561 are integral parts of a structural unit that we term the "kernel". Histidine to glutamine substitutions in the cytoplasmic-side heme center, but not in the matrix-side heme center, led to the retention of a small fraction of the low-potential heme with g z = 3.7. We provisionally assign the low-potential heme to the matrix side of the membrane; this arrangement suggests that the membrane potential modulates electron transport across the CG membrane.Most, if not all, eukaryotic organisms carry a gene for at least one member of the newly discovered protein family of cytochrome b 561 (cyt b 561 ) 1 (1-4). The oldest known member of the family, adrenal-type cyt b 561 , is essentially an ascorbate-regeneration machine (5) that plays a key role in supplying electrons for the biosynthesis of norepinephrine by dopamine-β-hydroxylase (6) and of several important peptide hormones by peptidylglycine β-monooxygenase (6). Several other cyt b 561 family members are either suggested to participate in ascorbate metabolism or to depend on ascorbate for ferric-reductase activity. Among them † This work was supported by American Heart Association (Texas Affiliate) Grant 0455107Y (G.P.), National Institutes of Health GM44911 (A-L.T.). * Address correspondence to these authors: Y. Kamensky, Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251, . E-mail: yuryk@bioc.rice.edu G. Palmer, Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251, USA. Telephone: 713-348-4860. FAX: 713-348-5154. E-mail: graham@bioc.rice.edu. 3 Our earlier publication (Kamensky, Y.A. and Palmer, G. (2001) Chromaffin granule membranes contain at least three heme centers, FEBS Lett. 491,) considered a third heme as either a cyt b 561 component or another heme-containing protein present in the CG membrane. That this third heme is not a part of cyt b 561 itself is now confirmed, as neither purified cyt b 561 from CG nor those expressed in insect, yeast or bac...

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Section: Identification Of Axial Ligands For Cyt B 561 Hemesmentioning

confidence: 91%

Axial Ligation and Stoichiometry of Heme Centers in Adrenal Cytochromeb₅₆₁

Kamensky

Tsai

et al. 2007

Biochemistry

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“…SDH, or succinate:menaquinone oxidoreductase, is another enzyme responsible for the donation of electrons to the quinone pool (13). Transposon mutagenesis confirmed that SDH is essential for survival of M. tuberculosis in vitro (24).…”

Section: Electron Donorsmentioning

confidence: 96%

“…1). Electron transport in mycobacteria is initiated through the activity of various NADH dehydrogenases (NDH) and succinate dehydrogenases (SDH), which transfer electrons to menaquinone, a lipophilic redox carrier (7,13,14). Electrons are then passed to various cytochrome oxidases, which are dependent on oxygen availability ( Fig.…”

Section: The Mycobacterial Etcmentioning

confidence: 99%

Energy Metabolism and Drug Efflux in Mycobacterium tuberculosis

Black

Warren

Louw

et al. 2014

Antimicrob Agents Chemother

117

102

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cThe inherent drug susceptibility of microorganisms is determined by multiple factors, including growth state, the rate of drug diffusion into and out of the cell, and the intrinsic vulnerability of drug targets with regard to the corresponding antimicrobial agent. Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains a significant source of global morbidity and mortality, further exacerbated by its ability to readily evolve drug resistance. It is well accepted that drug resistance in M. tuberculosis is driven by the acquisition of chromosomal mutations in genes encoding drug targets/promoter regions; however, a comprehensive description of the molecular mechanisms that fuel drug resistance in the clinical setting is currently lacking. In this context, there is a growing body of evidence suggesting that active extrusion of drugs from the cell is critical for drug tolerance. M. tuberculosis encodes representatives of a diverse range of multidrug transporters, many of which are dependent on the proton motive force (PMF) or the availability of ATP. This suggests that energy metabolism and ATP production through the PMF, which is established by the electron transport chain (ETC), are critical in determining the drug susceptibility of M. tuberculosis. In this review, we detail advances in the study of the mycobacterial ETC and highlight drugs that target various components of the ETC. We provide an overview of some of the efflux pumps present in M. tuberculosis and their association, if any, with drug transport and concomitant effects on drug resistance. The implications of inhibiting drug extrusion, through the use of efflux pump inhibitors, are also discussed.

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“…The ability to reduce hydrophobic quinones is conferred to the enzyme by a so-called membrane anchor subunit, whose structure and composition can vary significantly in different organisms (14,38). In B. subtilis, this subunit is a diheme cytochrome b (15), with the two porphyrin groups arranged across the membrane on top of each other, as predicted by mutagenesis studies (14,16) and confirmed recently by the three-dimensional crystal structure of complex II from Wolinella succinogenes (32,34). The low-potential heme b (approximately isopotential with MQ-MQH 2 [15,50]) is located close to the outer periplasmic side of the membrane and is believed to be the MQ reducing site (20,39,42,47,50).…”

mentioning

confidence: 83%

“…It is noted that the hypothesis of vectorial electron transfer through SQR is not necessarily compromised by our results. The membrane potential-driven reduction of MQ in B. subtilis SQR is predicted explicitly by the structure of the enzyme and therefore remains an attractive possibility (14,32,42), which, however, should not be confused or identified with the effect of energy-dependent stimulation of respiration.…”

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confidence: 99%

Stimulation of Menaquinone-Dependent Electron Transfer in the Respiratory Chain ofBacillus subtilisby Membrane Energization

Azarkina

Konstantinov

2002

J Bacteriol

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At a pH of <7, respiration of Bacillus subtilis cells on endogenous substrates shut down almost completely upon addition of an uncoupler (carbonyl cyanide m-chlorophenylhydrazone [CCCP]) and a K ؉ -ionophore (valinomycin). The same effect was observed with cell spheroplasts lacking the cell wall. The concentration of CCCP required for 50% inhibition of the endogenous respiration in the presence of K ؉ -valinomycin was below 100 nM. Either CCCP or valinomycin alone was much less efficient than the combination of the two. The inhibitory effect was easily reversible and depended specifically on the H ؉ and K ؉ concentrations in the medium. Similar inhibition was observed with respect to the reduction of the artificial electron acceptors 2,6-dichlorophenolindophenol (DCPIP) and N,N,N,N-tetramethyl-p-phenylenediamine cation (TMPD ؉ ), which intercept reducing equivalents at the level of menaquinol. Oxidation of the reduced DCPIP or TMPD in the bacterial cells was not sensitive to uncoupling. The same loss of the electron transfer activities as induced by the uncoupling was observed upon disruption of the cells during isolation of the membranes; the residual activities were not further inhibited by the uncoupler and ionophores. We conclude that the menaquinonedependent electron transfer in the B. subtilis respiratory chain is facilitated, thermodynamically or kinetically, by membrane energization. A requirement for an energized state of the membrane is not a specific feature of succinate oxidation, as proposed in the literature, since it was also observed in a mutant of B. subtilis lacking succinate:quinone reductase as well as for substrates other than succinate. Possible mechanisms of the energy-dependent regulation of menaquinone-dependent respiration in B. subtilis are discussed.There is a classical phenomenon of a so-called respiratory control in mitochondrial oxidative phosphorylation (35; reviewed in reference 18). Electron flow in the mitochondrial respiratory chain becomes slow as the membrane is energized (the state of respiratory control) and can be stimulated under these conditions by addition of ADP, which turns on ATP synthesis, or by the uncouplers of oxidative phosporylation, which dissipate the transmembrane electrochemical proton potential difference (⌬H ϩ ). Although described initially for mitochondria, the effect of respiratory control is often assumed to apply to bacterial coupled respiration as well (see, e.g., reference 43).It is therefore interesting that respiration of the aerobic bacterium Bacillus subtilis is stimulated rather than suppressed by proton motive force. The fact that the respiration of B. subtilis cells can be inhibited by K ϩ /H ϩ and Na ϩ /H ϩ antiporters and protonophores was noticed about 10 years ago (3, 37, 46) and confirmed more recently by Shirawski and Unden (47). A potentially relevant observation is that the succinate oxidase activity of B. subtilis cells decreases drastically during isolation of the membranes (36, 47); this effect could also be a consequence of memb...

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Succinate: quinone oxidoreductases: new insights from X-ray crystal structures

Cited by 63 publications

References 43 publications

Axial Ligation and Stoichiometry of Heme Centers in Adrenal Cytochromeb₅₆₁

Axial Ligation and Stoichiometry of Heme Centers in Adrenal Cytochromeb₅₆₁

Energy Metabolism and Drug Efflux in Mycobacterium tuberculosis

Stimulation of Menaquinone-Dependent Electron Transfer in the Respiratory Chain ofBacillus subtilisby Membrane Energization

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Succinate: quinone oxidoreductases: new insights from X-ray crystal structures

Cited by 63 publications

References 43 publications

Axial Ligation and Stoichiometry of Heme Centers in Adrenal Cytochromeb561

Axial Ligation and Stoichiometry of Heme Centers in Adrenal Cytochromeb561

Energy Metabolism and Drug Efflux in Mycobacterium tuberculosis

Stimulation of Menaquinone-Dependent Electron Transfer in the Respiratory Chain ofBacillus subtilisby Membrane Energization

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Axial Ligation and Stoichiometry of Heme Centers in Adrenal Cytochromeb₅₆₁

Axial Ligation and Stoichiometry of Heme Centers in Adrenal Cytochromeb₅₆₁