7KMU

Structure of WT Malaysian Banana Lectin

7KMU の概要

• エントリーDOI: 10.2210/pdb7kmu/pdb
• 分子名称: Jacalin-type lectin domain-containing protein, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: mannose-specific jacalin-related lectin, sugar binding protein
• 由来する生物種: Musa acuminata (Wild banana)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32808.66

構造登録者

Meagher, J.L.,Stuckey, J.A. (登録日: 2020-11-03, 公開日: 2021-01-27, 最終更新日: 2023-10-18)

主引用文献

Coves-Datson, E.M.,King, S.R.,Legendre, M.,Swanson, M.D.,Gupta, A.,Claes, S.,Meagher, J.L.,Boonen, A.,Zhang, L.,Kalveram, B.,Raglow, Z.,Freiberg, A.N.,Prichard, M.,Stuckey, J.A.,Schols, D.,Markovitz, D.M.
Targeted disruption of pi-pi stacking in Malaysian banana lectin reduces mitogenicity while preserving antiviral activity.
Sci Rep, 11:656-656, 2021

PubMed Abstract: Lectins, carbohydrate-binding proteins, have been regarded as potential antiviral agents, as some can bind glycans on viral surface glycoproteins and inactivate their functions. However, clinical development of lectins has been stalled by the mitogenicity of many of these proteins, which is the ability to stimulate deleterious proliferation, especially of immune cells. We previously demonstrated that the mitogenic and antiviral activities of a lectin (banana lectin, BanLec) can be separated via a single amino acid mutation, histidine to threonine at position 84 (H84T), within the third Greek key. The resulting lectin, H84T BanLec, is virtually non-mitogenic but retains antiviral activity. Decreased mitogenicity was associated with disruption of pi-pi stacking between two aromatic amino acids. To examine whether we could provide further proof-of-principle of the ability to separate these two distinct lectin functions, we identified another lectin, Malaysian banana lectin (Malay BanLec), with similar structural features as BanLec, including pi-pi stacking, but with only 63% amino acid identity, and showed that it is both mitogenic and potently antiviral. We then engineered an F84T mutation expected to disrupt pi-pi stacking, analogous to H84T. As predicted, F84T Malay BanLec (F84T) was less mitogenic than wild type. However, F84T maintained strong antiviral activity and inhibited replication of HIV, Ebola, and other viruses. The F84T mutation disrupted pi-pi stacking without disrupting the overall lectin structure. These findings show that pi-pi stacking in the third Greek key is a conserved mitogenic motif in these two jacalin-related lectins BanLec and Malay BanLec, and further highlight the potential to rationally engineer antiviral lectins for therapeutic purposes.

PubMed: 33436903
DOI: 10.1038/s41598-020-80577-7

実験手法

X-RAY DIFFRACTION (1.51 Å)