| Structural highlights
6wmn is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , , |
| Related: | |
| Gene: | B3GNT2, B3GALT7, B3GNT1 (HUMAN) |
| Activity: | Transferase, with EC number 2.4.1.149 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[B3GN2_HUMAN] Beta-1,3-N-acetylglucosaminyltransferase involved in the synthesis of poly-N-acetyllactosamine. Catalyzes the initiation and elongation of poly-N-acetyllactosamine chains. Shows a marked preference for Gal(beta1-4)Glc(NAc)-based acceptors (PubMed:9892646). Probably constitutes the main polylactosamine synthase.[1] [2] [3]
Publication Abstract from PubMed
Poly-N-acetyl-lactosamine (poly-LacNAc) structures are composed of repeating [-Galbeta(1,4)-GlcNAcbeta(1,3)-]n glycan extensions. They are found on both N- and O--glycoproteins and glycolipids, and play an important role in development, immune function, and human disease. The majority of mammalian poly-LacNAc is synthesized by the alternating iterative action of beta1,3-N-acetylglucosaminyltransferase 2 (B3GNT2) and beta1,4-galactosyltransferases. B3GNT2 is in the largest mammalian glycosyltransferase family, GT31, but little is known about the structure, substrate recognition, or catalysis by family members. Here we report the structures of human B3GNT2 in complex with UDP:Mg(2+), and in complex with both UDP:Mg(2+) and a glycan acceptor, lacto-N-neotetraose. The B3GNT2 structure conserves the GT-A fold and the DxD motif that coordinates a Mg(2+) ion for binding the UDP-GlcNAc sugar donor. The acceptor complex shows interactions with only the terminal Galbeta(1,4)-GlcNAcbeta(1,3)- disaccharide unit, which likely explains the specificity for both N- and O-glycan acceptors. Modeling of the UDP-GlcNAc donor supports a direct displacement inverting catalytic mechanism. Comparative structural analysis indicates that nucleotide sugar donors for GT-A fold glycosyltransferases bind in similar positions and conformations without conserving interacting residues, even for enzymes that use the same donor substrate. In contrast, the B3GNT2 acceptor binding site is consistent with prior models suggesting that the evolution of acceptor specificity involves loops inserted into the stable GT-A fold. These observations support the hypothesis that GT-A fold glycosyltransferases employ co-evolving donor, acceptor, and catalytic subsite modules as templates to achieve the complex diversity of glycan linkages in biological systems.
Comparison of human poly-N-acetyl-lactosamine synthase structure with GT-A fold glycosyltransferases supports a modular assembly of catalytic subsites.,Kadirvelraj R, Yang JY, Kim HW, Sanders JH, Moremen KW, Wood ZA J Biol Chem. 2020 Nov 23. pii: RA120.015305. doi: 10.1074/jbc.RA120.015305. PMID:33229435[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shiraishi N, Natsume A, Togayachi A, Endo T, Akashima T, Yamada Y, Imai N, Nakagawa S, Koizumi S, Sekine S, Narimatsu H, Sasaki K. Identification and characterization of three novel beta 1,3-N-acetylglucosaminyltransferases structurally related to the beta 1,3-galactosyltransferase family. J Biol Chem. 2001 Feb 2;276(5):3498-507. doi: 10.1074/jbc.M004800200. Epub 2000, Oct 19. PMID:11042166 doi:http://dx.doi.org/10.1074/jbc.M004800200
- ↑ Praissman JL, Live DH, Wang S, Ramiah A, Chinoy ZS, Boons GJ, Moremen KW, Wells L. B4GAT1 is the priming enzyme for the LARGE-dependent functional glycosylation of alpha-dystroglycan. Elife. 2014 Oct 3;3. doi: 10.7554/eLife.03943. PMID:25279697 doi:http://dx.doi.org/10.7554/eLife.03943
- ↑ Zhou D, Dinter A, Gutierrez Gallego R, Kamerling JP, Vliegenthart JF, Berger EG, Hennet T. A beta-1,3-N-acetylglucosaminyltransferase with poly-N-acetyllactosamine synthase activity is structurally related to beta-1,3-galactosyltransferases. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):406-11. doi: 10.1073/pnas.96.2.406. PMID:9892646 doi:http://dx.doi.org/10.1073/pnas.96.2.406
- ↑ Kadirvelraj R, Yang JY, Kim HW, Sanders JH, Moremen KW, Wood ZA. Comparison of human poly-N-acetyl-lactosamine synthase structure with GT-A fold glycosyltransferases supports a modular assembly of catalytic subsites. J Biol Chem. 2020 Nov 23. pii: RA120.015305. doi: 10.1074/jbc.RA120.015305. PMID:33229435 doi:http://dx.doi.org/10.1074/jbc.RA120.015305
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