Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Anopheles gambiae odorant binding protein crystal complex with the synthetic repellent DEET: implications for structure-based design of novel mosquito repellents
Δημιουργός/Συγγραφέας:	Tsitsanou, K. E. Thireou, T. Drakou, C. E. Koussis, K. Keramioti, M. V. [EL] Λεωνίδας, Δημήτρης Δ.[EN] Leonidas, Demetres D. Eliopoulos, E. Iatrou, K. [EL] Ζωγράφος, Σπύρος Ε.[EN] Zographos, Spyros E.
Εκδότης:	Springer Basel Ag
Τόπος έκδοσης:	Basel
Ημερομηνία:	2012-01
Γλώσσα:	Αγγλικά
ISSN:	1420-682X
DOI:	10.1007/s00018-011-0745-z
Περίληψη:	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 mu Ie) 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.
Τίτλος πηγής δημοσίευσης:	Cellular and Molecular Life Sciences Birkhauser
Τόμος/Κεφάλαιο:	69
Τεύχος:	2
Σελίδες:	283-297
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General)
Λέξεις-Κλειδιά:	Crystal structure Molecular modeling AgamOBP1 DEET Malaria
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
EU Grant identifier:	info:eu-repo/grantAgreement/EC/FP7/245866 info:eu-repo/grantAgreement/EC/FP7/222927 info:eu-repo/grantAgreement/EC/FP7/230146
Κάτοχος πνευματικών δικαιωμάτων:	© SPRINGER BASEL AG
Ηλεκτρονική διεύθυνση περιοδικού (link) :	http://www.springerlink.com/openurl.asp?genre=journal&issn=1420-682X
ΙΒΦΧΒ: αρχειακή συλλογή:	Ινστιτούτο Οργανικής και Φαρμακευτικής Χημείας (ΙΟΦΧ) (έως 2012)
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο