Structural and evolutionary divergence of cyclic nucleotide binding domains in eukaryotic pathogens: Implications for drug design.
Biochim Biophys Acta
; 1854(10 Pt B): 1575-85, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-25847873
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas
/
Estructura Terciaria de Proteína
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Evolución Molecular
/
Interacciones Huésped-Patógeno
Límite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos