Mode of action of famoxadone

Jordan, Douglas B.; Livingston, Robert S.; Bisaha, John J.; Duncan, Keith E; Pember, Stephen O.; Picollelli, Michael A; Schwartz, Rand S.; Sternberg, Jeffrey A.; Tang, Xiao-Song

doi:10.1002/(sici)1096-9063(199902)55:2<105::aid-ps879>3.0.co;2-d

Cited by 78 publications

(22 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tyr 279 has been postulated to participate in the positioning of the substrate ubiquinol (6). Alanine, serine, and cysteine replacements resulted in a distinct decrease of catalytic turnover (18,25, and 55% of wild-type turnover, respectively). Apparently, the mutations make QCR a limiting step in respiratory growth, since the doubling times of the mutants increased Ն2-fold.…”

Section: Discussionsupporting

confidence: 70%

“…The side chain of Phe 129 is in hydrophobic interaction with the tail of stigmatellin and probably with that of the substrate. This residue is a locus of center P inhibitor resistance both in yeast and bacterial QCR (17)(18)(19). Mutational analysis of the equivalent residue in bacterial QCR (Phe 144 ) indicated that replacement of Phe 144 affects ubiquinol binding and oxidation (9).…”

Section: /Ementioning

confidence: 99%

See 1 more Smart Citation

Mutational Analysis of Cytochrome b at the Ubiquinol Oxidation Site of Yeast Complex III

Wenz

Covián

Hellwig

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

The cytochrome bc 1 complex is a dimeric enzyme of the inner mitochondrial membrane that links electron transfer from ubiquinol to cytochrome c by a protonmotive Q cycle mechanism in which ubiquinol is oxidized at one center in the enzyme, referred to as center P, and ubiquinone is rereduced at a second center, referred to as center N. To better understand the mechanism of ubiquinol oxidation, we have examined catalytic activities and pre-steady-state reduction kinetics of yeast cytochrome bc 1 complexes with mutations in cytochrome b that we expected would affect oxidation of ubiquinol. We mutated two residues thought to be involved in proton conduction linked to ubiquinol oxidation, Tyr 132 and Glu 272 , and two residues proposed to be involved in docking ubiquinol into the center P pocket, Phe

show abstract

Section: Discussionsupporting

confidence: 70%

Section: /Ementioning

confidence: 99%

Mutational Analysis of Cytochrome b at the Ubiquinol Oxidation Site of Yeast Complex III

Wenz

Covián

Hellwig

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…It was reported that both the release and motility of zoospores are affected by energy generation inhibitors such as famoxadone and cyazofamid. 11,12) Thus, it is suggested that benthiavalicarb-isopropyl does not affect the energy production system of P. infestans. But benthiavalicarb-isopropyl prevents zoospores from encysting (data not shown).…”

Section: Indirect Germination From Zoosporangia and Motility Of Zoospmentioning

confidence: 99%

Fungicidial Activity of Benthiavalicarb-isopropyl against <i>Phytophthora infestans</i> and Its Controlling Activity against Late Blight Diseases

Miyake

Sakai

Shibata³

et al. 2005

Journal of Pesticide Science

View full text Add to dashboard Cite

“…2A) is an oxazolidinedione-type Q P site inhibitor (29). It has reportedly displayed various IC 50 values for submitochondrial particles from different species (30). However, evidence is mounting that some fungal species are intrinsically more resistant (30,31), and field applications of famoxadone for fungal disease control have led to rapid development of resistance that renders the inhibitor ineffective (32)(33)(34).…”

mentioning

confidence: 91%

Hydrogen Bonding to the Substrate Is Not Required for Rieske Iron-Sulfur Protein Docking to the Quinol Oxidation Site of Complex III

Esser

Zhou

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by Norma AllewellComplex III or the cytochrome (cyt) bc 1 complex constitutes an integral part of the respiratory chain of most aerobic organisms and of the photosynthetic apparatus of anoxygenic purple bacteria. The function of cyt bc 1 is to couple the reaction of electron transfer from ubiquinol to cytochrome c to proton pumping across the membrane. Mechanistically, the electron transfer reaction requires docking of its Rieske iron-sulfur protein (ISP) subunit to the quinol oxidation site (Q P ) of the complex. Formation of an H-bond between the ISP and the bound substrate was proposed to mediate the docking. Here we show that the binding of oxazolidinedione-type inhibitors famoxadone, jg144, and fenamidone induces docking of the ISP to the Q P site in the absence of the H-bond formation both in mitochondrial and bacterial cyt bc 1 complexes, demonstrating that ISP docking is independent of the proposed direct ISP-inhibitor interaction. The binding of oxazolidinedione-type inhibitors to cyt bc 1 of different species reveals a toxophore that appears to interact optimally with residues in the Q P site. The effect of modifications or additions to the toxophore on the binding to cyt bc 1 from different species could not be predicted from structure-based sequence alignments, as demonstrated by the altered binding mode of famoxadone to bacterial cyt bc 1 .The ubiquinol-cytochrome c oxidoreductase, also known as complex III of mitochondrial respiratory chain or cytochrome (cyt) 3 bc 1 complex, catalyzes the reaction of electron transfer (ET) from ubiquinol (QH 2 ) to cyt c and concomitantly translocates protons across the inner membrane of mitochondria or the plasma membrane of photosynthetic purple bacteria, contributing to a cross-membrane potential important for cellular function (1, 2). Although catalyzing the same enzymatic reaction, cyt bc 1 complexes isolated from different organisms have very different subunit compositions. Prokaryotic bc 1 complexes often consist of 3-4 subunits, whereas mitochondrial enzymes have 10 -11 different subunits (1). Nevertheless, only three subunits are essential for the ET function ( Fig. 1A): cyt b, cyt c 1 , and the Rieske iron-sulfur protein (ISP) (3). The cyt b subunit contains two b-type hemes, b L and b H , for the low and high potential hemes, respectively, and is entirely embedded in the membrane with eight transmembrane (TM) helices (4). The cyt c 1 subunit, anchored to the membrane by a single TM helix, has a c-type heme covalently attached to its active domain that is located in the intermembrane space of mitochondria or periplasm in bacteria. The ISP subunit features an integrated 2Fe-2S cluster in its extrinsic domain (ISP-ED) that is on the same side as the cyt c 1 subunit and also anchored to the membrane by a helix. The ET-coupled proton translocation function, as modeled by the Q-cycle mechanism (Fig. 1B), requires two active sites: a QH 2 oxidation (Q P ) site and a ubiquinone (Q) reduction (Q N ) site (5-7), which were shown to exist by crystal structu...

show abstract

Mode of action of famoxadone

Cited by 78 publications

References 20 publications

Mutational Analysis of Cytochrome b at the Ubiquinol Oxidation Site of Yeast Complex III

Mutational Analysis of Cytochrome b at the Ubiquinol Oxidation Site of Yeast Complex III

Fungicidial Activity of Benthiavalicarb-isopropyl against <i>Phytophthora infestans</i> and Its Controlling Activity against Late Blight Diseases

Hydrogen Bonding to the Substrate Is Not Required for Rieske Iron-Sulfur Protein Docking to the Quinol Oxidation Site of Complex III

Contact Info

Product

Resources

About