6TXR

Structural insights into cubane-modified aptamer recognition of a malaria biomarker

6TXR の概要

• エントリーDOI: 10.2210/pdb6txr/pdb
• 分子名称: L-lactate dehydrogenase, ~{N}-[2-(1,2,3-triazol-1-yl)ethyl]cubane-1-carboxamide, 2'-DEOXYGUANOSINE-5'-MONOPHOSPHATE, ... (7 entities in total)
• 機能のキーワード: aptamer, cubamer, pvldh, dna
• 由来する生物種: Plasmodium vivax (malaria parasite P. vivax)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 161146.16

構造登録者

Cheung, Y.,Roethlisberger, P.,Mechaly, A.,Weber, P.,Wong, A.,Lo, Y.,Haouz, A.,Savage, P.,Hollenstein, M.,Tanner, J. (登録日: 2020-01-14, 公開日: 2020-07-15, 最終更新日: 2024-01-24)

主引用文献

Cheung, Y.W.,Rothlisberger, P.,Mechaly, A.E.,Weber, P.,Levi-Acobas, F.,Lo, Y.,Wong, A.W.C.,Kinghorn, A.B.,Haouz, A.,Savage, G.P.,Hollenstein, M.,Tanner, J.A.
Evolution of abiotic cubane chemistries in a nucleic acid aptamer allows selective recognition of a malaria biomarker.
Proc.Natl.Acad.Sci.USA, 117:16790-16798, 2020

PubMed Abstract: Nucleic acid aptamers selected through systematic evolution of ligands by exponential enrichment (SELEX) fold into exquisite globular structures in complex with protein targets with diverse translational applications. Varying the chemistry of nucleotides allows evolution of nonnatural nucleic acids, but the extent to which exotic chemistries can be integrated into a SELEX selection to evolve nonnatural macromolecular binding interfaces is unclear. Here, we report the identification of a cubane-modified aptamer (cubamer) against the malaria biomarker lactate dehydrogenase (PvLDH). The crystal structure of the complex reveals an unprecedented binding mechanism involving a multicubane cluster within a hydrophobic pocket. The binding interaction is further stabilized through hydrogen bonding via cubyl hydrogens, previously unobserved in macromolecular binding interfaces. This binding mechanism allows discriminatory recognition of over lactate dehydrogenase, thereby distinguishing these highly conserved malaria biomarkers for diagnostic applications. Together, our data demonstrate that SELEX can be used to evolve exotic nucleic acids bearing chemical functional groups which enable remarkable binding mechanisms which have never been observed in biology. Extending to other exotic chemistries will open a myriad of possibilities for functional nucleic acids.

PubMed: 32631977
DOI: 10.1073/pnas.2003267117

実験手法

X-RAY DIFFRACTION (2.5 Å)