کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1177733 962576 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structural and evolutionary divergence of cyclic nucleotide binding domains in eukaryotic pathogens: Implications for drug design
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Structural and evolutionary divergence of cyclic nucleotide binding domains in eukaryotic pathogens: Implications for drug design
چکیده انگلیسی

Many cellular functions in eukaryotic pathogens are mediated by the cyclic nucleotide binding (CNB) domain, which senses second messengers such as cyclic AMP and cyclic GMP. Although CNB domain-containing proteins have been identified in many pathogenic organisms, an incomplete understanding of how CNB domains in pathogens differ from other eukaryotic hosts has hindered the development of selective inhibitors for CNB domains associated with infectious diseases. Here, we identify and classify CNB domain-containing proteins in eukaryotic genomes to understand the evolutionary basis for CNB domain functional divergence in pathogens. We identify 359 CNB domain-containing proteins in 31 pathogenic organisms and classify them into distinct subfamilies based on sequence similarity within the CNB domain as well as functional domains associated with the CNB domain. Our study reveals novel subfamilies with pathogen-specific variations in the phosphate-binding cassette. Analyzing these variations in light of existing structural and functional data provides new insights into ligand specificity and promiscuity and clues for drug design. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics - Volume 1854, Issue 10, Part B, October 2015, Pages 1575–1585
نویسندگان
, , , , , , ,