ABCC8 p.Leu266Met
| Predicted by SNAP2: | A: D (63%), C: N (57%), D: D (80%), E: D (75%), F: N (72%), G: D (71%), H: D (75%), I: N (66%), K: D (75%), M: N (66%), N: D (75%), P: D (80%), Q: D (71%), R: D (75%), S: D (71%), T: D (66%), V: D (59%), W: D (71%), Y: D (63%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: N, Y: N, |
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[hide] Molecular modeling of glycosyltransferases involve... Glycobiology. 2003 May;13(5):377-86. Epub 2003 Jan 22. Heissigerova H, Breton C, Moravcova J, Imberty A
Molecular modeling of glycosyltransferases involved in the biosynthesis of blood group A, blood group B, Forssman, and iGb3 antigens and their interaction with substrates.
Glycobiology. 2003 May;13(5):377-86. Epub 2003 Jan 22., [PMID:12626391]
Abstract [show]
A terminal alpha1-3 linked Gal or GalNAc sugar residue is the common structure found in several oligosaccharide antigens, such as blood groups A and B, the xeno-antigen, the Forssman antigen, and the isogloboside 3 (iGb3) glycolipid. The enzymes involved in the addition of this residue display strong amino acid sequence similarities, suggesting a common fold. From a recently solved crystal structure of the bovine alpha3-galactosyltransferase complexed with UDP, homology modeling methods were used to build the four other enzymes of this family in their locked conformation. Nucleotide-sugars, the Mn2+ ion, and oligosaccharide acceptors were docked in the models. Nine different amino acid regions are involved in the substrate binding sites. After geometry optimization of the complexes and analysis of the predicted structures, the basis of the specificities can be rationalized. In the nucleotide-sugar binding site, the specificity between Gal or GalNAc transferase activity is due to the relative size of two clue amino acids. In the acceptor site, the presence of up to three tryptophan residues define the complexity of the oligosaccharide that can be specifically recognized. The modeling study helps in rationalizing the crystallographic data obtained in this family and provides insights on the basis of substrate and donor recognition.
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No. Sentence Comment
154 Comparison with biochemical data on GTA and GTB The differences in amino acids between GTA and GTB are limited to four residues: Arg176Gly, Gly235Ser, Leu266Met, and Gly268Ala (Yamamoto et al., 1990).
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ABCC8 p.Leu266Met 12626391:154:151
status: NEW156 As discussed, Leu266Met and Gly268Ala substitutions (region LBR-E) have a crucial effect on the shape of the nucleotide binding pocket and directly affect the specificity for the nucleotide sugar.
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ABCC8 p.Leu266Met 12626391:156:14
status: NEW[hide] Fold recognition study of alpha3-galactosyltransfe... Glycobiology. 1999 Jul;9(7):713-22. Imberty A, Monier C, Bettler E, Morera S, Freemont P, Sippl M, Flockner H, Ruger W, Breton C
Fold recognition study of alpha3-galactosyltransferase and molecular modeling of the nucleotide sugar-binding domain.
Glycobiology. 1999 Jul;9(7):713-22., [PMID:10362841]
Abstract [show]
The structure and fold of the enzyme responsible for the biosynthesis of the xenotransplantation antigen, namely pig alpha3 galactosyltransferase, has been studied by means of computational methods. Secondary structure predictions indicated that alpha3-galactosyltransferase and related protein family members, including blood group A and B transferases and Forssman synthase, are likely to consist of alternating alpha-helices and beta-strands. Fold recognition studies predicted that alpha3-galactosyltransferase shares the same fold as the T4 phage DNA-modifying enzyme beta-glucosyltransferase. This latter enzyme displays a strong structural resemblance with the core of glycogen phosphorylase b. By using the three-dimensional structure of beta-glucosyltransferase and of several glycogen phosphorylases, the nucleotide binding domain of pig alpha3-galactosyltransferase was built by knowledge-based methods. Both the UDP-galactose ligand and a divalent cation were included in the model during the refinement procedure. The final three-dimensional model is in agreement with our present knowledge of the biochemistry and mechanism of alpha3-galactosyltransferases.
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No. Sentence Comment
53 Only four amino acids differ between bgA and bgB, i.e., Arg176Gly, Gly235Ser, Leu266Met,andGly268Ala(Yamamotoetal.,1990),thetwolast ones being the more crucial in determining nucleotide-sugar specificity (Yamamoto and Hakamori, 1990; Seto et al., 1997).
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ABCC8 p.Leu266Met 10362841:53:78
status: NEW152 One intriguing question is why do the Leu266Met and Gly268Ala mutations alter the specificity from blood group A to blood group B, i.e., from a GalNAc to a Gal-transferase.
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ABCC8 p.Leu266Met 10362841:152:38
status: NEW