title: Not an exception to the rule: the functional significance of intrinsically disordered protein regions in enzymes.
abstract: Intrinsically disordered protein regions (IDPRs) are remarkably common and have unique and important biological functions. Enzymes have long been considered an exception to the rule of protein intrinsic disorder due to the structural requirements for catalysis. Although functionally significant IDPRs have been described in several enzymes, there has been no study quantifying the extent of this phenomenon. We have conducted a multilevel computational analysis of missing regions in X-ray crystal structures in the PDB and predicted disorder in 66 representative proteomes. We found that the fraction of predicted disorder was higher in non-enzymes than enzymes, because non-enzymes were more likely to be fully disordered. However, we also found that transferases, hydrolases and enzymes with multiple assigned functional classifications were similar to non-enzymes in terms of the length of the longest continuous stretch of predicted disorder. Both eukaryotic enzymes and non-enzymes had a greater disorder content than was seen in bacteria. Disorder at the proteome level appears to emerge in response to organismic and functional complexity, and enzymes are not an exception to this rule.
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida 33612, USA. vuversky@health.usf.edu sdeforte@health.usf.edu.
authors.forename: Shelly
authors.initials: S
authors.lastname: DeForte
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida 33612, USA. vuversky@health.usf.edu sdeforte@health.usf.edu and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida 33612, USA and Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russian Federation.
authors.forename: Vladimir N
authors.identifier: http://orcid.org/0000-0002-4037-5857
authors.initials: VN
authors.lastname: Uversky
mesh_terms: D001419:Bacteria / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism; D056890:Eukaryota / Q000378:metabolism; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D013329:Structure-Activity Relationship
chemical_list: D004798:Enzymes; D064267:Intrinsically Disordered Proteins