title: Prediction of Spontaneous Protein Deamidation from Sequence-Derived Secondary Structure and Intrinsic Disorder.
abstract: Asparagine residues in proteins undergo spontaneous deamidation, a post-translational modification that may act as a molecular clock for the regulation of protein function and turnover. Asparagine deamidation is modulated by protein local sequence, secondary structure and hydrogen bonding. We present NGOME, an algorithm able to predict non-enzymatic deamidation of internal asparagine residues in proteins in the absence of structural data, using sequence-based predictions of secondary structure and intrinsic disorder. Compared to previous algorithms, NGOME does not require three-dimensional structures yet yields better predictions than available sequence-only methods. Four case studies of specific proteins show how NGOME may help the user identify deamidation-prone asparagine residues, often related to protein gain of function, protein degradation or protein misfolding in pathological processes. A fifth case study applies NGOME at a proteomic scale and unveils a correlation between asparagine deamidation and protein degradation in yeast. NGOME is freely available as a webserver at the National EMBnet node Argentina, URL: http://www.embnet.qb.fcen.uba.ar/ in the subpage "Protein and nucleic acid structure and sequence analysis".
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors.forename: J Ramiro
authors.initials: JR
authors.lastname: Lorenzo
authors.affiliation: Protein Structure-Function and Engineering Laboratory, Fundación Instituto Leloir and IIBBA-CONICET, Buenos Aires, Argentina.
authors.forename: Leonardo G
authors.initials: LG
authors.lastname: Alonso
authors.affiliation: Protein Physiology Laboratory, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales and IQUIBICEN-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Ignacio E
authors.initials: IE
authors.lastname: Sánchez
mesh_terms: D000577:Amides / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D001216:Asparagine / Q000737:chemistry; D006801:Humans; D016899:Interferon-beta / Q000737:chemistry / Q000378:metabolism; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D020539:Sequence Analysis, Protein / Q000379:methods*; D012984:Software; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism; D051020:bcl-X Protein / Q000737:chemistry / Q000378:metabolism
chemical_list: D000577:Amides; D064267:Intrinsically Disordered Proteins; D029701:Saccharomyces cerevisiae Proteins; D051020:bcl-X Protein; D001216:Asparagine; D016899:Interferon-beta; D013482:Superoxide Dismutase