4D11

GalNAc-T2 crystal soaked with UDP-5SGalNAc, mEA2 peptide and manganese (Lower resolution dataset)

Summary for 4D11

• Entry DOI: 10.2210/pdb4d11/pdb
• Related: 4D0T 4D0Z
• Descriptor: POLYPEPTIDE GALNAC-TRANSFERASE T2, PEPTIDE, MANGANESE (II) ION, ... (6 entities in total)
• Functional Keywords: transferase-peptide complex, retaining galnac-t2, substrate-guided sni-type reaction, qm/mm metadynamics, bi-bi kinetic mechanism, substrate specificity, acetamido group, transferase/peptide
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 11
• Total formula weight: 395424.98

Authors

Lira-Navarrete, E.,Iglesias-Fernandez, J.,Zandberg, W.F.,Companon, I.,Kong, Y.,Corzana, F.,Pinto, B.M.,Clausen, H.,Peregrina, J.M.,Vocadlo, D.,Rovira, C.,Hurtado-Guerrero, R. (deposition date: 2014-05-01, release date: 2014-05-28, Last modification date: 2024-11-13)

Primary citation

Lira-Navarrete, E.,Iglesias-Fernandez, J.,Zandberg, W.F.,Companon, I.,Kong, Y.,Corzana, F.,Pinto, B.M.,Clausen, H.,Peregrina, J.M.,Vocadlo, D.,Rovira, C.,Hurtado-Guerrero, R.
Substrate-Guided Front-Face Reaction Revealed by Combined Structural Snapshots and Metadynamics for the Polypeptide N- Acetylgalactosaminyltransferase 2.
Angew.Chem.Int.Ed.Engl., 53:8206-, 2014

PubMed Abstract: The retaining glycosyltransferase GalNAc-T2 is a member of a large family of human polypeptide GalNAc-transferases that is responsible for the post-translational modification of many cell-surface proteins. By the use of combined structural and computational approaches, we provide the first set of structural snapshots of the enzyme during the catalytic cycle and combine these with quantum-mechanics/molecular-mechanics (QM/MM) metadynamics to unravel the catalytic mechanism of this retaining enzyme at the atomic-electronic level of detail. Our study provides a detailed structural rationale for an ordered bi-bi kinetic mechanism and reveals critical aspects of substrate recognition, which dictate the specificity for acceptor Thr versus Ser residues and enforce a front-face SN i-type reaction in which the substrate N-acetyl sugar substituent coordinates efficient glycosyl transfer.

PubMed: 24954443
DOI: 10.1002/ANIE.201402781

Experimental method

X-RAY DIFFRACTION (2.85 Å)