7V4Z

Structure of Horcolin native form

7V4Z の概要

• エントリーDOI: 10.2210/pdb7v4z/pdb
• 分子名称: Horcolin, GLYCEROL, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: horcolin, mannose-binding lectin, sugar binding protein
• 由来する生物種: Hordeum vulgare (Barley)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 184381.76

構造登録者

Bobbili, K.B.,Sivaji, N.,Jayaprakash, N.G.,Narayanan, V.,Sekhar, A.,Suguna, K.,Surolia, A. (登録日: 2021-08-16, 公開日: 2022-03-09, 最終更新日: 2023-11-29)

主引用文献

Narayanan, V.,Bobbili, K.B.,Sivaji, N.,Jayaprakash, N.G.,Suguna, K.,Surolia, A.,Sekhar, A.
Structure and Carbohydrate Recognition by the Nonmitogenic Lectin Horcolin.
Biochemistry, 61:464-478, 2022

PubMed Abstract: Lectins are sugar-binding proteins that have shown considerable promise as antiviral agents because of their ability to interact with envelope glycoproteins present on the surface of viruses such as HIV-1. However, their therapeutic potential has been compromised by their mitogenicity that stimulates uncontrolled division of T-lymphocytes. Horcolin, a member of the jacalin family of lectins, tightly binds the HIV-1 envelope glycoprotein gp120 and neutralizes HIV-1 particles but is nonmitogenic. In this report, we combine X-ray crystallography and NMR spectroscopy to obtain atomic-resolution insights into the structure of horcolin and the molecular basis for its carbohydrate recognition. Each protomer of the horcolin dimer adopts a canonical β-prism I fold with three Greek key motifs and carries two carbohydrate-binding sites. The carbohydrate molecule binds in a negatively charged pocket and is stabilized by backbone and side chain hydrogen bonds to conserved residues in the ligand-binding loop. NMR titrations reveal a two-site binding mode and equilibrium dissociation constants for the two binding sites determined from two-dimensional (2D) lineshape modeling are 4-fold different. Single-binding-site variants of horcolin confirm the dichotomy in binding sites and suggest that there is allosteric communication between the two sites. An analysis of the horcolin structure shows a network of hydrogen bonds linking the two carbohydrate-binding sites directly and through a secondary binding site, and this coupling between the two sites is expected to assume importance in the interaction of horcolin with high-mannose glycans found on viral envelope glycoproteins.

PubMed: 35225598
DOI: 10.1021/acs.biochem.1c00778

実験手法

X-RAY DIFFRACTION (1.16 Å)