S-Adenosylhomocysteine hydrolase: an evolutionary analysis on the structure and sequence

سال انتشار: 1402
محل انتشار: دوازدهمین همایش ملی و سومین همایش بین المللی بیوانفورماتیک
کد COI اختصاصی: IBIS12_162
زبان مقاله: انگلیسی
تعداد مشاهده: 57

نویسندگان

Department of Cell and Molecular Biology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran

M.R Shams

Department of Animal and Plant Biology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran

M.R Ganjalikhany

Department of Cell and Molecular Biology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran

چکیده

S-Adenosylhomocysteine hydrolase (AHCY), one of the most conserved proteins involvedin the methionine cycle and converting S-adenosylhomocysteine (SAH), linked to cancer, heart disease,DNA damage, and prevention of DNA repair, to homocysteine (HCY) [۱-۴]. High levels of HCY leadsto oxidative stress, endoplasmic reticulum stress, and increased cell death [۵]. Evolutionary studies havesuggested the lateral transfer of the gene for the enzyme [۶], with its highly conserved protein presentin all domains of life and its potential as a drug target, encouraged us to delve into its evolutionary path.Employing Clustal Omega and TimeTree۵, comparative trees were constructed to illustrate theevolutionary emergence of both species and the enzyme. Regarding the limitations of the algorithms insimilar studies, we attempt to construct two other trees, using Maximum Likelihood and MinimumEvolution methods. Using TM-align, we compared the ۳D-structure of enzyme in human with ۱۱ otherorganisms. At the beginning of its evolutionary journey, the enzyme's overall length increased abruptlyand then gradually decreased, ۴۳۲ amino-acids in Human. Multiple sequence alignment revealed theabsent of two distinguished segments in the enzyme and low conservation in the N-terminal. Comparingenzyme phylogenetic trees to the Tree of Life demonstrates that their evolution does not follow theusual three-domain tree, suggesting either a potential for a lateral gene transfer between distancedorganisms or high pressure in selection duo to enzyme’s significance. Comparing Tm-scores revealsthat organisms from archaea domain show higher score than protozoa or bacteria. ۳D-structure analysisindicated changes in the C-terminal domain and a helix structure, in the NAD binding domain of Homosapiens, was missed from the surface. This study provides a wide range of analysis on AHCY as a vitalenzyme and its evolutionary dynamics. These novel perspectives improve our understanding ofstructural and, may functional evolution of AHCY.

کلیدواژه ها

S-Adenosylhomocysteine hydrolase; evolutionary analysis; phylogenetic tree

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