title: Functional evolution of PLP-dependent enzymes based on active-site structural similarities.
abstract: Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5'-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the comparison of protein active site structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional-fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS.
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, 68588-0304.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Catazaro
authors.forename: Adam
authors.initials: A
authors.lastname: Caprez
authors.forename: Ashu
authors.initials: A
authors.lastname: Guru
authors.forename: David
authors.initials: D
authors.lastname: Swanson
authors.forename: Robert
authors.initials: R
authors.lastname: Powers
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D003067:Coenzymes / Q000737:chemistry / Q000378:metabolism*; D030562:Databases, Protein; D019143:Evolution, Molecular; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D011732:Pyridoxal Phosphate / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012984:Software; D013379:Substrate Specificity; D000637:Transaminases / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism
chemical_list: D003067:Coenzymes; D008024:Ligands; D011732:Pyridoxal Phosphate; D000637:Transaminases
keywords: CPASS; PLP-dependent enzymes; functional evolution; ligand binding sites