بررسی توالی و ساختار مرکزی در ساختمان الکل دهیدروژنازها

نوع مقاله: مقاله پژوهشی

نویسندگان

1 استادیار/پژوهشگاه ملی مهندسی ژنتیک و زیست فناوری

2 استادیار/پزوهشگاه ملی و مهندسی ژنتیک و زیست فناوری

3 استادیار/دانشگاه تهران

4 دانشیار/دانشگاه اصفهان

چکیده

با هدف بررسی و شناسایی اسیدهای آمینه‌ مهم از نظر ساختاری و عملکردی در خانواده الکل دهیدروژنازها که در طول تکامل محافظت شده‌اند، تجزیه و تحلیل کامپیوتری پیشرفته‌ای بر روی توالی و ساختار سه بعدی این آنزیم‌ها انجام شد. آنالیزتوالی با توجه به برخی خصوصیات اسیدهای آمینه از جمله همسانی، تشابه، انتروپی، هیدروفوبیسیتی برای تعیین سطح محافظت شدگی در هر جایگاه انجام گرفت. بر اساس محاسبات انجام شده، مناطق بسیار محافظت شده‌ای در ساختار و توالی الکل دهیدروژنازها شناسایی شدند. با آنالیز بیشتر توالی‌ها و جایگاه‌های محافظت شده، معلوم شد که در این مناطق، خصوصیات مشترکی مشاهده می‌شود. نتایج محاسبات در این مطالعه نشان داد که این امکان وجود دارد که در جایگاه‌های ویژه‌ای از ساختار این آنزیم، الگوهای محافظت شده خاصی تعریف شود و بر آن اساس، پایداری ساختاری آنزیم که عامل غلبگی آن در طول تکامل است را توجیه کند. در این مطالعه دو منطقه کاملاٌ محافظت شده که الگوی مشخصی را در توالی خود در طول تکامل حفظ کرده‌اند، مشخص شدند. به نظر می‌رسد این موتیف ها در تغییر آرایش فضایی آنزیم بعد از اتصال به سوبسترا یک نقش مکانیکی به عنوان لولا داشته باشند.

کلیدواژه‌ها

عنوان مقاله [English]

Multivariant analysis of core structure in Alcohol Dehydrogenases

نویسندگان [English]

  • Shamila Alipoor Astaneh 1
  • Zarrin Minuchehr 2
  • Armin Madadkar-Sobhani 3
  • Mehran Miroliaei 4

1 Assistant Professor / National Institute of Genetics and Biotechnology

2 Assistant Professor / National Institute of Genetics and Biotechnology

3 Assistant Professor / University of Tehran

4 Associate professor / Isfahan University

چکیده [English]

A progressive computational analysis of available sequence and crystal structure data was used to identify functionally and structurally important residues in medium-chain Alcohol dehydrogenases super family throughout evolution. Altman and Gretsine core finding method was used to identify a core set of atoms with low structural variability. With further analysis of core regions in ADHs (solvent exposure and number of contacts) and also sequential analysis, we could infer the common properties of highly conserved positions in ADHs. The sequential analysis was done with respect to some special properties of amino acids in order to derive the level of conservation. The core structure analysis was re-judged in light of sequential analysis. Sixty percent of the core positions correspond to the highly conserved positions that were found by the sequence analysis.It seems that the core positions in ADHs are responsible for the maintenance of structural integrity and also contribute to the active site. Location of rigid parts of structures in catalytic domain may help to minimize the thermal fluctuation effect on substrate binding and would probably keep the structure in a good condition. Our data supports that it is possible to define patterns of conservity in some important region in sequence of Alcohol dehydrogenase and explain patterns of structural stability which are necessary for overcoming throughout evolution.

کلیدواژه‌ها [English]

  • Alcohol dehydrogenase
  • Core structure
  • Sequence analysis
  • Structure analysis
  • Conservation study
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