7V4S

Horcolin complex with methyl-alpha-mannose

Summary for 7V4S

• Entry DOI: 10.2210/pdb7v4s/pdb
• Descriptor: Horcolin, methyl alpha-D-mannopyranoside (3 entities in total)
• Functional Keywords: horcolin, mannose-binding lectin, sugar binding protein
• Biological source: Hordeum vulgare (Barley)
• Total number of polymer chains: 1
• Total formula weight: 15524.44

Authors

Bobbili, K.B.,Sivaji, N.,Jayaprakash, N.G.,Narayanan, V.,Sekhar, A.,Suguna, K.,Surolia, A. (deposition date: 2021-08-14, release date: 2022-03-09, Last modification date: 2023-11-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.2 Å)