4KC2

Structure of the blood group glycosyltransferase AAglyB in complex with a pyridine inhibitor as a neutral pyrophosphate surrogate

Summary for 4KC2

• Entry DOI: 10.2210/pdb4kc2/pdb
• Related: 4KC1 4KC4
• Descriptor: Fucosylglycoprotein alpha-N-acetylgalactosaminyltransferase soluble form, MANGANESE (II) ION, octyl 2-O-(6-deoxy-alpha-L-galactopyranosyl)-beta-D-galactopyranoside, ... (5 entities in total)
• Functional Keywords: gta superfamily, blood group proteins, glycosyltransferase, fuc-gal, udp-gal, udp-galnac, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Golgi apparatus, Golgi stack membrane; Single-pass type II membrane protein: P16442
• Total number of polymer chains: 1
• Total formula weight: 34768.94

Authors

Cuesta-Seijo, J.A.,Wang, S.,Lafont, D.,Vidal, S.,Palcic, M.M. (deposition date: 2013-04-24, release date: 2013-09-11, Last modification date: 2023-09-20)

Primary citation

Wang, S.,Cuesta-Seijo, J.A.,Lafont, D.,Palcic, M.M.,Vidal, S.
Design of glycosyltransferase inhibitors: pyridine as a pyrophosphate surrogate.
Chemistry, 19:15346-15357, 2013

PubMed Abstract: A series of ten glycosyltransferase inhibitors has been designed and synthesized by using pyridine as a pyrophosphate surrogate. The series was prepared by conjugation of carbohydrate, pyridine, and nucleoside building blocks by using a combination of glycosylation, the Staudinger-Vilarrasa amide-bond formation, and azide-alkyne click chemistry. The compounds were evaluated as inhibitors of five metal-dependent galactosyltransferases. Crystallographic analyses of three inhibitors complexed in the active site of one of the enzymes confirmed that the pyridine moiety chelates the Mn(2+) ion causing a slight displacement (2 Å) from its original position. The carbohydrate head group occupies a different position than in the natural uridine diphosphate (UDP)-Gal substrate with little interaction with the enzyme.

PubMed: 24108680
DOI: 10.1002/chem.201301871

Experimental method

X-RAY DIFFRACTION (1.7 Å)