کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2047629 1074006 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Crystal structure of the catalase–peroxidase KatG W78F mutant from Synechococcus elongatus PCC7942 in complex with the antitubercular pro-drug isoniazid
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش گیاه شناسی
پیش نمایش صفحه اول مقاله
Crystal structure of the catalase–peroxidase KatG W78F mutant from Synechococcus elongatus PCC7942 in complex with the antitubercular pro-drug isoniazid
چکیده انگلیسی


• Isoniazid, an anti-tuberculosis pro-drug, is activated by the KatG.
• Tryptophan 78 occupies the entrance at the γ-edge side of the heme.
• The structure of KatG-W78F reveals that an INH molecule binds in γ-edge of heme.
• One-residue substitution in SeKatG dramatically changed the INH binding site.

Isoniazid (INH) is a pro-drug that has been extensively used to treat tuberculosis. INH is activated by the heme enzyme catalase–peroxidase (KatG), but the mechanism of the activation is poorly understood, in part because the INH binding site has not been clearly established. Here, we observed that a single-residue mutation of KatG from Synechococcus elongatus PCC7942 (SeKatG), W78F, enhances INH activation. The crystal structure of INH-bound KatG-W78F revealed that INH binds to the heme pocket. The results of a thermal-shift assay implied that the flexibility of the SeKatG molecule is increased by the W78F mutation, allowing the INH molecule to easily invade the heme pocket through the access channel on the γ-edge side of the heme.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: FEBS Letters - Volume 589, Issue 1, 2 January 2015, Pages 131–137
نویسندگان
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