Sauter N K, Glick G D, Crowther R L, Park S J, Eisen M B, Skehel J J, Knowles J R, Wiley D C
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):324-8. doi: 10.1073/pnas.89.1.324.
X-ray crystal structures have been determined for several complexes between influenza virus hemagglutinin and derivatives of its cell-surface receptor, sialic acid (Neu5Ac). Difference electron density maps establish the existence of a second binding site in addition to the primary site characterized previously. Three compounds bind to both sites: Neu5Ac(alpha 2-3)Gal(beta 1-4)Glc [(alpha 2-3)sialyllactose], alpha-2-O-(4'-benzylamidocarboxybutyl)-5-N-acetylneuraminic acid, and alpha-2-O-(4'-methylamidocarboxybutyl)-5-N-acetylneuraminic acid; and four other compounds bind only to the primary site: Neu5Ac(alpha 2-6)Gal(beta 1-4)Glc [(alpha 2-6)sialyllactose], alpha-2-O-methyl-5-N-acetylneuraminic acid, 4-]-acetyl-alpha-2-O-methyl-5-N-acetylneuraminic acid, and 9-amino-9-deoxy-alpha-2-O-methyl-5-N-acetylneuraminic acid. The maps also extend earlier results by showing the location of all three sugar residues of (alpha 2-3)sialyllactose in the primary binding site. The affinity of (alpha 2-3)sialyllactose for the second site was estimated by collecting x-ray diffraction data at various ligand concentrations and was found to be at least four times weaker than its affinity for the primary site. Although it is not yet known whether the second binding site participates in the infection process, it nevertheless offers a potential target for the design of antiviral drugs.
已经确定了几种流感病毒血凝素与其细胞表面受体唾液酸（Neu5Ac）衍生物之间复合物的X射线晶体结构。差分电子密度图表明，除了先前表征的主要结合位点外，还存在第二个结合位点。三种化合物与两个位点都结合：Neu5Ac（α2-3）Gal（β1-4）Glc [（α2-3）唾液乳糖]、α-2-O-（4'-苄基酰胺基羧基丁基）-5-N-乙酰神经氨酸和α-2-O-（4'-甲基酰胺基羧基丁基）-5-N-乙酰神经氨酸；另外四种化合物仅与主要位点结合：Neu5Ac（α2-6）Gal（β1-4）Glc [（α2-6）唾液乳糖]、α-2-O-甲基-5-N-乙酰神经氨酸、4-O-乙酰基-α-2-O-甲基-5-N-乙酰神经氨酸和9-氨基-9-脱氧-α-2-O-甲基-5-N-乙酰神经氨酸。这些图谱还通过显示（α2-3）唾液乳糖的所有三个糖残基在主要结合位点中的位置扩展了早期结果。通过在各种配体浓度下收集X射线衍射数据，估计了（α2-3）唾液乳糖对第二个位点的亲和力，发现其比其对主要位点的亲和力至少弱四倍。虽然尚不清楚第二个结合位点是否参与感染过程，但它仍然为抗病毒药物的设计提供了一个潜在靶点。
