4ZBN

Non-helical DNA Triplex Forms a Unique Aptamer Scaffold for High Affinity Recognition of Nerve Growth Factor

4ZBN の概要

• エントリーDOI: 10.2210/pdb4zbn/pdb
• 分子名称: DNA (28-MER), Beta-nerve growth factor, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (4 entities in total)
• 機能のキーワード: complex, aptamer, immune system-dna complex, immune system/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Secreted: P01138
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 46860.50

構造登録者

Davies, D.R.,Edwards, T.E. (登録日: 2015-04-15, 公開日: 2015-06-10, 最終更新日: 2024-10-23)

主引用文献

Jarvis, T.C.,Davies, D.R.,Hisaminato, A.,Resnicow, D.I.,Gupta, S.,Waugh, S.M.,Nagabukuro, A.,Wadatsu, T.,Hishigaki, H.,Gawande, B.,Zhang, C.,Wolk, S.K.,Mayfield, W.S.,Nakaishi, Y.,Burgin, A.B.,Stewart, L.J.,Edwards, T.E.,Gelinas, A.D.,Schneider, D.J.,Janjic, N.
Non-helical DNA Triplex Forms a Unique Aptamer Scaffold for High Affinity Recognition of Nerve Growth Factor.
Structure, 23:1293-1304, 2015

PubMed Abstract: Discerning the structural building blocks of macromolecules is essential for understanding their folding and function. For a new generation of modified nucleic acid ligands (called slow off-rate modified aptamers or SOMAmers), we previously observed essential functions of hydrophobic aromatic side chains in the context of well-known nucleic acid motifs. Here we report a 2.45-Å resolution crystal structure of a SOMAmer complexed with nerve growth factor that lacks any known nucleic acid motifs, instead adopting a configuration akin to a triangular prism. The SOMAmer utilizes extensive hydrophobic stacking interactions, non-canonical base pairing and irregular purine glycosidic bond angles to adopt a completely non-helical, compact S-shaped structure. Aromatic side chains contribute to folding by creating an unprecedented intercalating zipper-like motif and a prominent hydrophobic core. The structure provides compelling rationale for potent inhibitory activity of the SOMAmer and adds entirely novel motifs to the repertoire of structural elements uniquely available to SOMAmers.

PubMed: 26027732
DOI: 10.1016/j.str.2015.03.027

実験手法

X-RAY DIFFRACTION (2.447 Å)