title: Identification of universal selectivity-determining positions in cytochrome P450 monooxygenases by systematic sequence-based literature mining.
abstract: Cytochrome P450 monooxygenases (CYPs) are a large, highly diverse protein family with a common fold. The sequences, structures, and functions of CYPs have been extensively studied resulting in more than 53,000 scientific articles. A sequence-based literature mining algorithm was designed to systematically analyze this wealth of information on SNPs, designed mutations, structural interactions, or functional roles of individual residues. Structurally corresponding positions in different CYPs were compared and universal selectivity-determining positions were identified. Based on the Cytochrome P450 Engineering Database (www.CYPED.BioCatNet.de) and a standard numbering scheme for all CYPs, 4000 residues in 168 CYPs mentioned in 2400 articles could be assigned to 440 structurally corresponding standard positions of the CYP fold, covering 96% of all standard positions. Seventeen individual standard positions were mentioned in the context of more than 32 different CYPs. The majority of these most frequently mentioned positions are located on the six substrate recognition sites and are involved in control of selectivity, such as the well-studied position 87 in CYP102A1 (P450(BM-3)) which was mentioned in the articles on 63 different CYPs. The recurrent citation of the 17 frequently mentioned positions for different CYPs suggests their universal functional relevance.
authors.affiliation: Institute of Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Gricman
authors.affiliation: Institute of Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: Vogel
authors.affiliation: Institute of Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Pleiss
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D057225:Data Mining / Q000379:methods*; D030561:Databases, Nucleic Acid; D030562:Databases, Protein; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System
keywords: CYP; data mining; database; hotspot; mutant