8A64
cryoEM structure of the catalytically inactive EndoS from S. pyogenes in complex with the Fc region of immunoglobulin G1.
This is a non-PDB format compatible entry.
Summary for 8A64
| Entry DOI | 10.2210/pdb8a64/pdb |
| EMDB information | 15205 |
| Descriptor | Endo-beta-N-acetylglucosaminidase F2, Immunoglobulin gamma-1 heavy chain, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | endoglycosidase s, endos, endo-b-n-acetylglucosaminidase, fc region, antibody, immunoglobulin g1, streptococcus pyogenes, n-glycans, hydrolase |
| Biological source | Streptococcus pyogenes More |
| Total number of polymer chains | 3 |
| Total formula weight | 207656.86 |
| Authors | Trastoy, B.,Cifuente, J.O.,Du, J.J.,Sundberg, E.J.,Guerin, M.E. (deposition date: 2022-06-16, release date: 2023-04-05, Last modification date: 2024-11-20) |
| Primary citation | Trastoy, B.,Du, J.J.,Cifuente, J.O.,Rudolph, L.,Garcia-Alija, M.,Klontz, E.H.,Deredge, D.,Sultana, N.,Huynh, C.G.,Flowers, M.W.,Li, C.,Sastre, D.E.,Wang, L.X.,Corzana, F.,Mallagaray, A.,Sundberg, E.J.,Guerin, M.E. Mechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases. Nat Commun, 14:1705-1705, 2023 Cited by PubMed Abstract: Bacterial pathogens have evolved intricate mechanisms to evade the human immune system, including the production of immunomodulatory enzymes. Streptococcus pyogenes serotypes secrete two multi-modular endo-β-N-acetylglucosaminidases, EndoS and EndoS2, that specifically deglycosylate the conserved N-glycan at Asn297 on IgG Fc, disabling antibody-mediated effector functions. Amongst thousands of known carbohydrate-active enzymes, EndoS and EndoS2 represent just a handful of enzymes that are specific to the protein portion of the glycoprotein substrate, not just the glycan component. Here, we present the cryoEM structure of EndoS in complex with the IgG1 Fc fragment. In combination with small-angle X-ray scattering, alanine scanning mutagenesis, hydrolytic activity measurements, enzyme kinetics, nuclear magnetic resonance and molecular dynamics analyses, we establish the mechanisms of recognition and specific deglycosylation of IgG antibodies by EndoS and EndoS2. Our results provide a rational basis from which to engineer novel enzymes with antibody and glycan selectivity for clinical and biotechnological applications. PubMed: 36973249DOI: 10.1038/s41467-023-37215-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.6 Å) |
Structure validation
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