کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8299114 | 1537052 | 2008 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Exploring the inhibitor binding pocket of respiratory complex I
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کلمات کلیدی
ubiquinonehexaammineruthenium(III)-chlorideYarrowia lipolytican-decylubiquinonePMSFDQADBQC12E8TRISMOPSHAR - اندInhibitor - بازدارندهTris(hydroxymethyl)aminomethane - تریس (هیدروکسی متیل) آمینومتانSMP - دانشکده دبیرستانdNADH - دسامبرSubmitochondrial particles - ذرات ریزRotenone - روتنونphenylmethylsulfonyl fluoride - فنیل متیل سولفونیل فلورایدComplex I - مجتمع IMutagenesis - موتاژنزMitochondria - میتوکندریا
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم کشاورزی و بیولوژیک
دانش گیاه شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Numerous hydrophobic and amphipathic compounds including several detergents are known to inhibit the ubiquinone reductase reaction of respiratory chain complex I (proton pumping NADH:ubiquinone oxidoreductase). Guided by the X-ray structure of the peripheral arm of complex I from Thermus thermophilus we have generated a large collection of site-directed mutants in the yeast Yarrowia lipolytica targeting the proposed ubiquinone and inhibitor binding pocket of this huge multiprotein complex at the interface of the 49-kDa and PSST subunits. We could identify a number of residues where mutations changed I50 values for representatives from all three groups of hydrophobic inhibitors. Many mutations around the domain of the 49-kDa subunit that is homologous to the [NiFe] centre binding region of hydrogenase conferred resistance to DQA (class I/type A) and rotenone (class II/type B) indicating a wider overlap of the binding sites for these two types of inhibitors. In contrast, a region near iron-sulfur cluster N2, where the binding of the n-alkyl-polyoxyethylene-ether detergent C12E8 (type C) was exclusively affected, appeared comparably well separated. Taken together, our data provide structure-based support for the presence of distinct but overlapping binding sites for hydrophobic inhibitors possibly extending into the ubiquinone reduction site of mitochondrial complex I.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Bioenergetics - Volume 1777, Issues 7â8, JulyâAugust 2008, Pages 660-665
Journal: Biochimica et Biophysica Acta (BBA) - Bioenergetics - Volume 1777, Issues 7â8, JulyâAugust 2008, Pages 660-665
نویسندگان
Uta Fendel, Maja A. Tocilescu, Stefan Kerscher, Ulrich Brandt,