1bcj
MANNOSE-BINDING PROTEIN-A MUTANT (QPDWGHV) COMPLEXED WITH N-ACETYL-D-GALACTOSAMINE
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OverviewOverview
The mammalian hepatic asialoglycoprotein receptor, a member of the C-type, animal lectin family, displays preferential binding to, N-acetylgalactosamine compared with galactose. The structural basis for, selective binding to N-acetylgalactosamine has been investigated. Regions, of the carbohydrate-recognition domain of the receptor believed to be, important in preferential binding to N-acetylgalactosamine have been, inserted into the homologous carbohydrate-recognition domain of a, mannose-binding protein mutant that was previously altered to bind, galactose. Introduction of a single histidine residue corresponding to, residue 256 of the hepatic asialoglycoprotein receptor was found to cause, a 14-fold increase in the relative affinity for N-acetylgalactosamine, compared with galactose. The relative ability of various acyl derivatives, of galactosamine to compete for binding to this modified, carbohydrate-recognition domain suggest that it is a good model for the, natural N-acetylgalactosamine binding site of the asialoglycoprotein, receptor. Crystallographic analysis of this mutant, carbohydrate-recognition domain in complex with N-acetylgalactosamine, reveals a direct interaction between the inserted histidine residue and, the methyl group of the N-acetyl substituent of the sugar. Evidence for, the role of the side chain at position 208 of the receptor in positioning, this key histidine residue was obtained from structural analysis and, mutagenesis experiments. The corresponding serine residue in the modified, carbohydrate-recognition domain of mannose-binding protein forms a, hydrogen bond to the imidazole side chain. When this serine residue is, changed to valine, loss in selectivity for N-acetylgalactosamine is, observed. The structure of this mutant reveals that the beta-branched, valine side chain interacts directly with the histidine side chain, resulting in an altered imidazole ring orientation.
About this StructureAbout this Structure
1BCJ is a Single protein structure of sequence from Rattus norvegicus with NGA, CA and CL as ligands. Structure known Active Sites: 11, 12, 13, 21, 22, 23, 31, 32 and 33. Full crystallographic information is available from OCA.
ReferenceReference
Mechanism of N-acetylgalactosamine binding to a C-type animal lectin carbohydrate-recognition domain., Kolatkar AR, Leung AK, Isecke R, Brossmer R, Drickamer K, Weis WI, J Biol Chem. 1998 Jul 31;273(31):19502-8. PMID:9677372
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