Recognition of fold and sugar linkage for glycosyltransferases by multivariate sequence analysis.
Glycosyltransferases (GTs) are among the largest groups of enzymes found and are usually classified on the basis of sequence comparisons into many families of varying similarity (CAZy systematics). Only two different Rossman-like folds have been detected (GT-A and GT-B) within the small number of established crystal structures. A third uncharacterized fold has been indicated with transmembrane organization (GT-C). We here use a method based on multivariate data analyses (MVDAs) of property patterns in amino acid sequences and can with high accuracy recognize the correct fold in a large data set of GTs. Likewise, a retaining or inverting enzymatic mechanism for attachment of the donor sugar could be properly revealed in the GT-A and GT-B fold group sequences by such analyses. Sequence alignments could be correlated to important variables in MVDA, and the separating amino acid positions could be mapped over the active sites. These seem to be localized to similar positions in space for the alpha/beta/alpha binding motifs in the GT-B fold group structures. Analogous, active-site sequence positions were found for the GT-A fold group. Multivariate property patterns could also easily group most GTs annotated in the genomes of Escherichia coli and Synechocystis to proper fold or organization group, according to benchmarking comparisons at the MetaServer. We conclude that the sequence property patterns revealed by the multivariate analyses seem more conserved than amino acid types for these GT groups, and these patterns are also conserved in the structures. Such patterns may also potentially define substrate preferences.
Rosén
Maria L
ML
Department of Biochemistry & Biophysics, Stockholm University, SE 106 91 Stockholm, Sweden.
Edman
Maria
M
Sjöström
Michael
M
Wieslander
Ake
A
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry*; D018360:Crystallography, X-Ray; D000458:Cyanobacteria / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D016680:Genome, Bacterial; D016695:Glycosyltransferases / Q000737:chemistry / Q000235:genetics*; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D016366:Open Reading Frames; D011487:Protein Conformation; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid
D002241:Carbohydrates; D016695:Glycosyltransferases