Sequence-Function Relationships of Prokaryotic and Eukaryotic Galactosyltransferases

Abstract

Galactosyltransferases are enzymes which transfer galactose from UDP-Gal to various acceptors with either retention of the anomeric configuration to form alpha1,2-, alpha1,3-, alpha1,4-, and alpha1, 6-linkages, or inversion of the anomeric configuration to form beta1, 3-, beta1,4-, and beta1-ceramide linkages. During the last few years, several (c)DNA sequences coding for galactosyltransferases became available. We have retrieved these sequences and conducted sequence similarity studies. On the basis of both the nature of the reaction catalyzed and the protein sequence identity, these enzymes can be classified into twelve groups. Using a sensitive graphics method for protein comparison, conserved structural features were found in some of the galactosyltransferase groups, and other classes of glycosyltransferases, resulting in the definition of five families. The lengths and locations of the conserved regions as well as the invariant residues are described for each family. In addition, the DxD motif that may be important for substrate recognition and/or catalysis is demonstrated to occur in all families but one.

A Membrane-located Glycosyltransferase Complex Required for Biosynthesis of the d-Galactan I Lipopolysaccharide O Antigen in Klebsiella pneumoniae

“…The frameshift mutation of wbbN in the D-galactan I cluster eliminated formation of D-galactan I, a result entirely consistent with WbbN being a galactosyltransferase involved in the overall chain extension process. In this family of GT enzymes, a DXD motif binds a catalytically important divalent metal ion (40,41). Site-directed changes of the identified DXD motif (in WbbN this is DDD) to AAA eliminate its activity as expected (data not shown).…”

Discovery of Streptococcus pneumoniae Serotype 6 Variants with Glycosyltransferases Synthesizing Two Differing Repeating Units

“…WciN␣ belongs to Pfam01501, which includes many glycosyltransferases used by viruses, bacteria, and eukaryotes and has the DXD motif well known for binding divalent cations (35,36). A mutation of residue 38 of WciN␣ is present in only one of the two German strains, and its neighboring residues are not conserved among Pfam01501 members.…”

Structures of 5-Methylthioribose Kinase Reveal Substrate Specificity and Unusual Mode of Nucleotide Binding

“…This motif appears functionally analogous to the DXD motif found in many glycosyltransferases. In glycosyltransferases this motif is involved in coordinating the nucleotide sugar donor-Mn(II) complex (47) and is important for transferase activity (48,49). The DXE motif is not found in protein kinases or the evolutionarily related eukaryotic-like kinases.…”