3N7H

Crystal structure of Odorant Binding Protein 1 from Anopheles gambiae (AgamOBP1) with DEET (N,N-Diethyl-meta-toluamide) and PEG

3N7H の概要

• エントリーDOI: 10.2210/pdb3n7h/pdb
• 関連するPDBエントリー: 2ERB
• 分子名称: Odorant binding protein, MAGNESIUM ION, METHANOL, ... (7 entities in total)
• 機能のキーワード: transport protein, insect odorant binding protein, obp1, agamobp1, deet, n, n-diethyl-meta-toluamide, olfaction
• 由来する生物種: Anopheles gambiae (African malaria mosquito)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32296.55

構造登録者

Tsitsanou, K.E.,Zographos, S.E. (登録日: 2010-05-27, 公開日: 2011-06-08, 最終更新日: 2024-11-27)

主引用文献

Tsitsanou, K.E.,Thireou, T.,Drakou, C.E.,Koussis, K.,Keramioti, M.V.,Leonidas, D.D.,Eliopoulos, E.,Iatrou, K.,Zographos, S.E.
Anopheles gambiae odorant binding protein crystal complex with the synthetic repellent DEET: implications for structure-based design of novel mosquito repellents.
Cell.Mol.Life Sci., 69:283-297, 2012

PubMed Abstract: Insect odorant binding proteins (OBPs) are the first components of the olfactory system to encounter and bind attractant and repellent odors emanating from various sources for presentation to olfactory receptors, which trigger relevant signal transduction cascades culminating in specific physiological and behavioral responses. For disease vectors, particularly hematophagous mosquitoes, repellents represent important defenses against parasitic diseases because they effect a reduction in the rate of contact between the vectors and humans. OBPs are targets for structure-based rational approaches for the discovery of new repellent or other olfaction inhibitory compounds with desirable features. Thus, a study was conducted to characterize the high resolution crystal structure of an OBP of Anopheles gambiae, the African malaria mosquito vector, in complex with N,N-diethyl-m-toluamide (DEET), one of the most effective repellents that has been in worldwide use for six decades. We found that DEET binds at the edge of a long hydrophobic tunnel by exploiting numerous non-polar interactions and one hydrogen bond, which is perceived to be critical for DEET's recognition. Based on the experimentally determined affinity of AgamOBP1 for DEET (K (d) of 31.3 μΜ) and our structural data, we modeled the interactions for this protein with 29 promising leads reported in the literature to have significant repellent activities, and carried out fluorescence binding studies with four highly ranked ligands. Our experimental results confirmed the modeling predictions indicating that structure-based modeling could facilitate the design of novel repellents with enhanced binding affinity and selectivity.

PubMed: 21671117
DOI: 10.1007/s00018-011-0745-z

実験手法

X-RAY DIFFRACTION (1.6 Å)