PDBsum entry 3n7h

Transport protein

PDB id: 3n7h

Contents

Protein chains

125 a.a.

Ligands

MOH ×8

DE3 ×2

PEU ×2

Metals

_MG ×2

_CL ×2

Waters ×349

PDB id:

3n7h

Name:

Transport protein

Title:

Crystal structure of odorant binding protein 1 from anopheles gambiae (agamobp1) with deet (n,n-diethyl-meta-toluamide) and peg

Structure:

Odorant binding protein. Chain: a, b. Fragment: unp residues 20-144. Engineered: yes

Source:

Anopheles gambiae. African malaria mosquito. Organism_taxid: 7165. Gene: agamobp1, obp-1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.60Å R-factor: 0.174 R-free: 0.203

Authors:

K.E.Tsitsanou,S.E.Zographos

Key ref:

K.E.Tsitsanou et al. (2012). 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. PubMed id: 21671117

Date:

27-May-10 Release date: 08-Jun-11

Protein chains

Q8T6S0  (Q8T6S0_ANOGA) -  Odorant binding protein from Anopheles gambiae

Seq: 144 a.a.

Struc: 125 a.a.

Cell Mol Life Sci 69:283-297 (2012)

PubMed id: 21671117

Anopheles gambiae odorant binding protein crystal complex with the synthetic repellent DEET: implications for structure-based design of novel mosquito repellents.

K.E.Tsitsanou, T.Thireou, C.E.Drakou, K.Koussis, M.V.Keramioti, D.D.Leonidas, E.Eliopoulos, K.Iatrou, S.E.Zographos.

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.