Three-dimensional structures of the Mn and Mg dTDP complexes of the family GT-2 glycosyltransferase SpsA: a comparison with related NDP-sugar glycosyltransferases.
The vast majority of glycosidic-bond synthesis in nature is performed by glycosyltransferases, which use activated glycosides as the sugar donor. Typically, the activated leaving group is a nucleoside phosphate, lipid phosphate or phosphate. The nucleotide-sugar-dependent glycosyltransferases fall into over 50 sequence-based families, with the largest and most widespread family of inverting transferases named family GT-2. Here, we present the three-dimensional crystal structure of SpsA, the first and currently the only structural representative from family GT-2, in complex with both Mn-dTDP and Mg-dTDP at a resolution of 2 A. These structures reveal how SpsA and related enzymes may display nucleotide plasticity and permit a comparison of the catalytic centre of this enzyme with those from related sequence families whose three-dimensional structures have recently been determined. Family GT-2 enzymes, together with enzymes from families 7, 13 and 43, appear to form a clan of related structures with identical catalytic apparatus and reaction mechanism.
Tarbouriech
N
N
Department of Chemistry, Structural Biology Laboratory, Heslington, Y010 5DD, UK.
Charnock
S J
SJ
Davies
G J
GJ
D001412:Bacillus subtilis / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D016695:Glycosyltransferases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D013942:Thymine Nucleotides / Q000378:metabolism*; D014530:Uridine Diphosphate / Q000378:metabolism
D001426:Bacterial Proteins; C110344:SpsA protein, Streptococcus pneumoniae; D013942:Thymine Nucleotides; D008345:Manganese; C027923:thymidine 5'-diphosphate; D014530:Uridine Diphosphate; D016695:Glycosyltransferases; D008274:Magnesium