title: Molecular signatures-based prediction of enzyme promiscuity.
abstract: BACKGROUND
  Enzyme promiscuity, a property with practical applications in biotechnology and synthetic biology, has been related to the evolvability of enzymes. At the molecular level, several structural mechanisms have been linked to enzyme promiscuity in enzyme families. However, it is at present unclear to what extent these observations can be generalized. Here, we introduce for the first time a method for predicting catalytic and substrate promiscuity using a graph-based representation known as molecular signature.
  
  
  RESULTS
  Our method, which has an accuracy of 85% for the non-redundant KEGG database, is also a powerful analytical tool for characterizing structural determinants of protein promiscuity. Namely, we found that signatures with higher contribution to the prediction of promiscuity are uniformly distributed in the protein structure of promiscuous enzymes. In contrast, those signatures that act as promiscuity determinants are significantly depleted around non-promiscuous catalytic sites. In addition, we present the study of the enolase and aminotransferase superfamilies as illustrative examples of characterization of promiscuous enzymes within a superfamily and achievement of enzyme promiscuity by protein reverse engineering. Recognizing the role of enzyme promiscuity in the process of natural evolution of enzymatic function can provide useful hints in the design of directed evolution experiments. We have developed a method with potential applications in the guided discovery and enhancement of latent catalytic capabilities surviving in modern enzymes.
  
  
  BACKGROUND
  http://www.issb.genopole.fr~faulon.
authors.affiliation: iSSB, Institute of Systems and Synthetic Biology, University of Evry, Evry, France. pcarbonell@issb.genopole.fr
authors.forename: Pablo
authors.initials: P
authors.lastname: Carbonell
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Faulon
mesh_terms: D001185:Artificial Intelligence; D002384:Catalysis; D020134:Catalytic Domain; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism; D015202:Protein Engineering; D011506:Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D004798:Enzymes; D011506:Proteins