Limits...
The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold.

Zhang H, Zhu F, Yang T, Ding L, Zhou M, Li J, Haslam SM, Dell A, Erlandsen H, Wu H - Nat Commun (2014)

Bottom Line: Structural studies, however, have only revealed two distinct glycosyltransferase (GT) folds, GT-A and GT-B.Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis.Thus, DUF1792 represents a new family of glycosyltransferases; therefore, we designate it as a GT-D glycosyltransferase fold.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pediatric Dentistry, Microbiology, Schools of Dentistry and Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

ABSTRACT
More than 33,000 glycosyltransferases have been identified. Structural studies, however, have only revealed two distinct glycosyltransferase (GT) folds, GT-A and GT-B. Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. DUF1792 homologues from both Gram-positive and Gram-negative bacteria also exhibit the activity. Thus, DUF1792 represents a new family of glycosyltransferases; therefore, we designate it as a GT-D glycosyltransferase fold. As the domain is highly conserved in bacteria and not found in eukaryotes, it can be explored as a new antibacterial target.

Show MeSH
The overall structure of DUF1792 (DUF1972-Mn)(a) Stereo image of the backbone trace of DUF1792. The alpha helices are colored cyan, the beta-strands are colored magenta, and coiled regions are salmon and the UDP molecule at the active site is shown in blue and the Mn-atom in orange.(b) Representative 2Fo-Fc electron density for DUF1792-Mn. Electron density for the helical region between residue 223–233 is shown in gray and contoured at 2sigma.(c) The overall structure of UDP and Mn-bound DUF1792. The manganese ion is colored orange, the UDP molecule is blue, beta-strands are magenta, alpha-helices are cyan, and coiled regions are salmon. Two acetate ions are found at the active site and are colored green. The secondary structural elements are shown in the figure on the left. Three views are shown (left, middle and right).(d) Archetypical GT-A type glycosyltransferase(PDB id code 1FOA).(e) Archetypical GT-B type glycosyltransferase(PDB id code 1J39).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4352575&req=5

Figure 5: The overall structure of DUF1792 (DUF1972-Mn)(a) Stereo image of the backbone trace of DUF1792. The alpha helices are colored cyan, the beta-strands are colored magenta, and coiled regions are salmon and the UDP molecule at the active site is shown in blue and the Mn-atom in orange.(b) Representative 2Fo-Fc electron density for DUF1792-Mn. Electron density for the helical region between residue 223–233 is shown in gray and contoured at 2sigma.(c) The overall structure of UDP and Mn-bound DUF1792. The manganese ion is colored orange, the UDP molecule is blue, beta-strands are magenta, alpha-helices are cyan, and coiled regions are salmon. Two acetate ions are found at the active site and are colored green. The secondary structural elements are shown in the figure on the left. Three views are shown (left, middle and right).(d) Archetypical GT-A type glycosyltransferase(PDB id code 1FOA).(e) Archetypical GT-B type glycosyltransferase(PDB id code 1J39).

Mentions: To further characterize this highly conserved new family of glycosyltransferases, we solved the X-ray crystal structure of DUF1792 from S. parasanguinis. The structure of DUF1792 was built by selenomethionyl substituted protein X-ray data utilizing the MAD method (Table 1). Both native protein (Native-DUF1792) and the native protein in complex with Mn (DUF1792-Mn) crystallize in a space group of C2 and exist as a monomer. In the native structure, a UDP molecule and one acetate ion were found (Supplementary Fig. 3). In the DUF1792-Mn structure, a UDP, a manganese and two acetate ions were present (Fig. 5a and c).


The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold.

Zhang H, Zhu F, Yang T, Ding L, Zhou M, Li J, Haslam SM, Dell A, Erlandsen H, Wu H - Nat Commun (2014)

The overall structure of DUF1792 (DUF1972-Mn)(a) Stereo image of the backbone trace of DUF1792. The alpha helices are colored cyan, the beta-strands are colored magenta, and coiled regions are salmon and the UDP molecule at the active site is shown in blue and the Mn-atom in orange.(b) Representative 2Fo-Fc electron density for DUF1792-Mn. Electron density for the helical region between residue 223–233 is shown in gray and contoured at 2sigma.(c) The overall structure of UDP and Mn-bound DUF1792. The manganese ion is colored orange, the UDP molecule is blue, beta-strands are magenta, alpha-helices are cyan, and coiled regions are salmon. Two acetate ions are found at the active site and are colored green. The secondary structural elements are shown in the figure on the left. Three views are shown (left, middle and right).(d) Archetypical GT-A type glycosyltransferase(PDB id code 1FOA).(e) Archetypical GT-B type glycosyltransferase(PDB id code 1J39).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352575&req=5

Figure 5: The overall structure of DUF1792 (DUF1972-Mn)(a) Stereo image of the backbone trace of DUF1792. The alpha helices are colored cyan, the beta-strands are colored magenta, and coiled regions are salmon and the UDP molecule at the active site is shown in blue and the Mn-atom in orange.(b) Representative 2Fo-Fc electron density for DUF1792-Mn. Electron density for the helical region between residue 223–233 is shown in gray and contoured at 2sigma.(c) The overall structure of UDP and Mn-bound DUF1792. The manganese ion is colored orange, the UDP molecule is blue, beta-strands are magenta, alpha-helices are cyan, and coiled regions are salmon. Two acetate ions are found at the active site and are colored green. The secondary structural elements are shown in the figure on the left. Three views are shown (left, middle and right).(d) Archetypical GT-A type glycosyltransferase(PDB id code 1FOA).(e) Archetypical GT-B type glycosyltransferase(PDB id code 1J39).
Mentions: To further characterize this highly conserved new family of glycosyltransferases, we solved the X-ray crystal structure of DUF1792 from S. parasanguinis. The structure of DUF1792 was built by selenomethionyl substituted protein X-ray data utilizing the MAD method (Table 1). Both native protein (Native-DUF1792) and the native protein in complex with Mn (DUF1792-Mn) crystallize in a space group of C2 and exist as a monomer. In the native structure, a UDP molecule and one acetate ion were found (Supplementary Fig. 3). In the DUF1792-Mn structure, a UDP, a manganese and two acetate ions were present (Fig. 5a and c).

Bottom Line: Structural studies, however, have only revealed two distinct glycosyltransferase (GT) folds, GT-A and GT-B.Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis.Thus, DUF1792 represents a new family of glycosyltransferases; therefore, we designate it as a GT-D glycosyltransferase fold.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pediatric Dentistry, Microbiology, Schools of Dentistry and Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

ABSTRACT
More than 33,000 glycosyltransferases have been identified. Structural studies, however, have only revealed two distinct glycosyltransferase (GT) folds, GT-A and GT-B. Here we report a 1.34-Å resolution X-ray crystallographic structure of a previously uncharacterized 'domain of unknown function' 1792 (DUF1792) and show that the domain adopts a new fold and is required for glycosylation of a family of serine-rich repeat streptococcal adhesins. Biochemical studies reveal that the domain is a glucosyltransferase, and it catalyses the transfer of glucose to the branch point of the hexasaccharide O-linked to the serine-rich repeat of the bacterial adhesin, Fap1 of Streptococcus parasanguinis. DUF1792 homologues from both Gram-positive and Gram-negative bacteria also exhibit the activity. Thus, DUF1792 represents a new family of glycosyltransferases; therefore, we designate it as a GT-D glycosyltransferase fold. As the domain is highly conserved in bacteria and not found in eukaryotes, it can be explored as a new antibacterial target.

Show MeSH