| Structural highlights
5ajp is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Related: | 5ajn, 5ajo |
| Activity: | Polypeptide N-acetylgalactosaminyltransferase, with EC number 2.4.1.41 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[GALT2_HUMAN] Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spectrum of substrates for peptides such as EA2, Muc5AC, Muc1a, Muc1b. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region.[1] [2]
Publication Abstract from PubMed
Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide specificity and catalysis remains unclear. Here we present the first crystal structures of complexes of GalNAc-T2 with glycopeptides that together with enhanced sampling molecular dynamics simulations demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Atomic force microscopy and small-angle X-ray scattering experiments further reveal a dynamic conformational landscape of GalNAc-T2 and a prominent role of compact structures that are both required for efficient catalysis. Our model indicates that the activity profile of GalNAc-T2 is dictated by conformational heterogeneity and relies on a flexible linker located between the catalytic and the lectin domains. Our results also shed light on how GalNAc-Ts generate dense decoration of proteins with O-glycans.
Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation.,Lira-Navarrete E, de Las Rivas M, Companon I, Pallares MC, Kong Y, Iglesias-Fernandez J, Bernardes GJ, Peregrina JM, Rovira C, Bernado P, Bruscolini P, Clausen H, Lostao A, Corzana F, Hurtado-Guerrero R Nat Commun. 2015 May 5;6:6937. doi: 10.1038/ncomms7937. PMID:25939779[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wandall HH, Hassan H, Mirgorodskaya E, Kristensen AK, Roepstorff P, Bennett EP, Nielsen PA, Hollingsworth MA, Burchell J, Taylor-Papadimitriou J, Clausen H. Substrate specificities of three members of the human UDP-N-acetyl-alpha-D-galactosamine:Polypeptide N-acetylgalactosaminyltransferase family, GalNAc-T1, -T2, and -T3. J Biol Chem. 1997 Sep 19;272(38):23503-14. PMID:9295285
- ↑ Iwasaki H, Zhang Y, Tachibana K, Gotoh M, Kikuchi N, Kwon YD, Togayachi A, Kudo T, Kubota T, Narimatsu H. Initiation of O-glycan synthesis in IgA1 hinge region is determined by a single enzyme, UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 2. J Biol Chem. 2003 Feb 21;278(8):5613-21. Epub 2002 Nov 15. PMID:12438318 doi:http://dx.doi.org/10.1074/jbc.M211097200
- ↑ Lira-Navarrete E, de Las Rivas M, Companon I, Pallares MC, Kong Y, Iglesias-Fernandez J, Bernardes GJ, Peregrina JM, Rovira C, Bernado P, Bruscolini P, Clausen H, Lostao A, Corzana F, Hurtado-Guerrero R. Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation. Nat Commun. 2015 May 5;6:6937. doi: 10.1038/ncomms7937. PMID:25939779 doi:http://dx.doi.org/10.1038/ncomms7937
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