1HGI

BINDING OF INFLUENZA VIRUS HEMAGGLUTININ TO ANALOGS OF ITS CELL-SURFACE RECEPTOR, SIALIC ACID: ANALYSIS BY PROTON NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY AND X-RAY CRYSTALLOGRAPHY

1HGI の概要

• エントリーDOI: 10.2210/pdb1hgi/pdb
• 分子名称: HEMAGGLUTININ, CHAIN HA1, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: influenza virus hemagglutinin, viral protein
• 由来する生物種: Influenza A virus; 詳細
• 細胞内の位置: Virion membrane; Single-pass type I membrane protein (Potential): P03437 P03437
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 174343.54

構造登録者

Sauter, N.K.,Hanson, J.E.,Glick, G.D.,Brown, J.H.,Crowther, R.L.,Park, S.-J.,Skehel, J.J.,Wiley, D.C. (登録日: 1991-11-01, 公開日: 1994-01-31, 最終更新日: 2020-07-29)

主引用文献

Sauter, N.K.,Hanson, J.E.,Glick, G.D.,Brown, J.H.,Crowther, R.L.,Park, S.J.,Skehel, J.J.,Wiley, D.C.
Binding of influenza virus hemagglutinin to analogs of its cell-surface receptor, sialic acid: analysis by proton nuclear magnetic resonance spectroscopy and X-ray crystallography.
Biochemistry, 31:9609-9621, 1992

PubMed Abstract: The interaction between influenza virus hemagglutinin and its cell-surface receptor, 5-N-acetylneuraminic acid (sialic acid), was probed by the synthesis of 12 sialic acid analogs, including derivatives at the 2-carboxylate, 5-acetamido, 4-, 7-, and 9-hydroxyl, and glycosidic positions. The equilibrium dissociation constants of these analogs were determined by nuclear magnetic resonance spectroscopy. Ligand modifications that reduced or abolished binding included the replacement of the 2-carboxylate with a carboxamide, the substitution of azido or N-benzyloxycarbonyl groups for the 5-acetamido group, and the replacement of the 9-hydroxyl with amino or O-acetyl moieties. Modifications having little effect on binding included the introduction of longer chains at the 4-hydroxyl position, the replacement of the acetamido methyl group with an ethyl group, and the removal of the 7-hydroxyl group. X-ray diffraction studies yielded 3 A resolution crystal structures of hemagglutinin in complex with four of the synthetic analogs [alpha-2-O-methyl-, 4-O-acetyl-alpha-2-O-methyl-, 9-amino-9-deoxy-alpha-2-O-methyl-, and alpha-2-O-(4'-benzylamidocarboxybutyl)-N-acetylneuraminic acid] and with the naturally occurring cell-surface saccharide (alpha 2-3)sialyllactose. The X-ray studies unambiguously establish the position and orientation of bound sialic acid, indicate the position of the lactose group of (alpha 2-3)sialyllactose, and suggest the location of an alpha-glycosidic chain (4'-benzylamidocarboxybutyl) that increases the binding affinity of sialic acid by a factor of about 3. Although the protein complexed with alpha-2-O-methylsialic acid contains the mutation Gly-135-->Arg near the ligand binding site, the mutation apparently does not affect the ligand's position. The X-ray studies allow us to interpret the binding affinities in terms of the crystallographic structure. The results suggest further experiments which could lead to the design of tight binding inhibitors of possible therapeutic value.

PubMed: 1327122
DOI: 10.1021/bi00155a013

実験手法

X-RAY DIFFRACTION (2.7 Å)