title: Lysine carboxylation: unveiling a spontaneous post-translational modification.
abstract: The carboxylation of lysine residues is a post-translational modification (PTM) that plays a critical role in the catalytic mechanisms of several important enzymes. It occurs spontaneously under certain physicochemical conditions, but is difficult to detect experimentally. Its full impact is unknown. In this work, the signature microenvironment of lysine-carboxylation sites has been characterized. In addition, a computational method called Predictor of Lysine Carboxylation (PreLysCar) for the detection of lysine carboxylation in proteins with available three-dimensional structures has been developed. The likely prevalence of lysine carboxylation in the proteome was assessed through large-scale computations. The results suggest that about 1.3% of large proteins may contain a carboxylated lysine residue. This unexpected prevalence of lysine carboxylation implies an enrichment of reactions in which it may play functional roles. The results also suggest that by switching enzymes on and off under appropriate physicochemical conditions spontaneous PTMs may serve as an important and widely used efficient biological machinery for regulation.
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, 851 South Morgan Street, Room 218, Chicago, IL 60607, USA.
authors.forename: David
authors.initials: D
authors.lastname: Jimenez-Morales
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, 851 South Morgan Street, Room 218, Chicago, IL 60607, USA.
authors.forename: Larisa
authors.initials: L
authors.lastname: Adamian
authors.affiliation: Children's National Medical Center, Center for Genetic Medicine Research, 111 Michigan Avenue NW, Washington, DC 20010-2970, USA.
authors.forename: Dashuang
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, 851 South Morgan Street, Room 218, Chicago, IL 60607, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
mesh_terms: D000465:Algorithms; D000818:Animals; D019295:Computational Biology; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D006801:Humans; D008239:Lysine / Q000032:analysis* / Q000378:metabolism; D008958:Models, Molecular; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011506:Proteins; D008239:Lysine
keywords: PreLysCar; Predictor of Lysine Carboxylation; lysine carboxylation; metal-ion centers; spontaneous post-translational modifications; structural motif