skip to main content

Title: Lysine carboxylation: unveiling a spontaneous post-translational modification

A computational method for the prediction of lysine carboxylation (KCX) in protein structures is described. The method accurately identifies misreported KCXs and predicts previously unknown KCX sites. 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:
;  [1] ;  [2] ;  [1]
  1. University of Illinois at Chicago, 851 South Morgan Street, Room 218, Chicago, IL 60607 (United States)
  2. Center for Genetic Medicine Research, 111 Michigan Avenue NW, Washington, DC 20010-2970 (United States)
Publication Date:
OSTI Identifier:
22351302
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section D: Biological Crystallography; Journal Volume: 70; Journal Issue: Pt 1; Other Information: PMCID: PMC3919261; PMID: 24419378; PUBLISHER-ID: lv5045; OAI: oai:pubmedcentral.nih.gov:3919261; Copyright (c) International Union of Crystallography 2014; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
Denmark
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; FORECASTING; IRON; LYSINE; MODIFICATIONS; PROTEIN STRUCTURE