title: The (betaalpha)(8) glycosidases: sequence and structure analyses suggest distant evolutionary relationships.
abstract: There are currently at least nine distinct glycosidase sequence families which are all known to adopt a TIM barrel fold [Henrissat,B. and Davies,G. (1997) CURR: Opin. Struct. Biol., 7, 637-644]. To explore the relationships between these enzymes and their evolution, comprehensive sequence and structure comparisons were performed, generating four distinct clusters. The first cluster, S1, comprises the alpha-amylase related enzymes, all with the retention mechanism (axial-->axial). The second cluster, S2, included two functional subgroups, one composed of various kinds of glucosidases all with the retention mechanism (equatorial-->equatorial) (the so-called 4/7 superfamily), and the other subgroup including the beta-amylases with the inversion mechanism (axial--> equatorial). The third cluster, S3, with the retention mechanism (equatorial-->equatorial), could be subdivided, based on the catalytic residues and mechanisms, into two functional subgroups: the chitinase group, catalysed by two acidic residues on the C-termini of beta-4 and beta-6, and the hevamine group, using two acidic residues on the C-termini of beta-4 for catalysis. The fourth cluster, S4, is composed of chitobiase with the retention mechanism (equatorial--> equatorial). These clusters are compared with the sequence families derived by Henrissat and coworkers. PSI-BLAST profiles and multiple-alignments of tertiary structures suggest that S1 and S2 are distantly related, as are S3 and S4, which have N-acetylated substrates. This work highlights the difficulties of untangling distant evolutionary relationships in ubiquitous folds such as the TIM barrel.
authors.affiliation: Biomolecular Structure and Modelling Group, Biochemistry & Molecular Biology Department, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: N
authors.initials: N
authors.lastname: Nagano
authors.forename: C T
authors.initials: CT
authors.lastname: Porter
authors.forename: J M
authors.initials: JM
authors.lastname: Thornton
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D002384:Catalysis; D020134:Catalytic Domain; D016000:Cluster Analysis; D019992:Databases as Topic; D019143:Evolution, Molecular; D006026:Glycoside Hydrolases / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D012984:Software
chemical_list: D006026:Glycoside Hydrolases