کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7608965 | 1493391 | 2018 | 37 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Structure-based design and application of a nucleotide coenzyme mimetic ligand: Application to the affinity purification of nucleotide dependent enzymes
ترجمه فارسی عنوان
طراحی مبتنی بر ساختار و کاربرد یک لیگاند مینیمم کوآنزیم نوکلئوتیدی: استفاده از آنزیم های وابسته به نوکلئوتید
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کلمات کلیدی
کروماتوگرافی وابستگی، فرمید دهیدروژناز، طرح لیگاند، بیوانفورماتیک ساختاری، موتاژنز اختصاصی سایت،
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
چکیده انگلیسی
In the present study, a structure-based approach was exploited for the in silico design of a nucleotide coenzyme mimetic ligand. The enzyme formate dehydrogenase (FDH) was employed as a model in our study. The biomimetic ligand was designed and synthesized based on a tryptamine/3-aminopropylphosphonic acid bi-substituted 1,3,5-triazine (Trz) scaffold (Tra-Trz-3APP), which potentially mimics the interactions of NAD+-FDH complex. Molecular docking studies of the biomimetic ligand predicted that it can occupy the same binding site as the natural coenzyme. Molecular modeling and dynamics simulations revealed that the ligand binds in an energetically more stable pose in the FDH binding site, as it adopts a more twisty conformation, compared to the natural coenzyme. Study of the FDH/Tra-Trz-3APP-Sepharose interaction, through adsorption equilibrium studies and site-directed mutagenesis of selected FDH coenzyme binding residues, provided additional experimental evidences of the specificity of the interaction. The Tra-Trz-3APP-Sepharose biomimetic adsorbent was further evaluated towards a range of different dehydrogenases and was exploited for the development of a single-step purification protocol for FDH. The protocol afforded enzyme with high yield and purity, suitable for analytical and industrial purposes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography A - Volume 1535, 2 February 2018, Pages 88-100
Journal: Journal of Chromatography A - Volume 1535, 2 February 2018, Pages 88-100
نویسندگان
Marigianna Marinou, Dimitrios Platis, Farid S. Ataya, Evangelia Chronopoulou, Dimitrios Vlachakis, Nikolaos E. Labrou,