Supervisors info:
Μ. Μαυρή, Αναπλ. Καθηγ. Επιβλέπουσα, Α. Σιαφάκα-Καπάδαη Καθηγ., Σ. Ζωγράφος, Ερευνητής Β΄ΙΟΦΧ/ΕΙΕ
Summary:
OBP4 is included in the class of proteins which transport the odorants from the
air to the receptors that are expressed in the odorant neurons of the
chemosensory organ of insect. Their structural study may elucidate the way of
binding of molecules with insect-repellent properties and thus help the
development of lead compounds with improved affinity and specificity. Such
substances, that are incorporated in the physiological odorant function of the
mosquito, may probably decrease the insect’s recognizing ability of the human
target and consequently contribute effectively in the reduction of the malaria
transmission. In the frame of this master thesis the structures of OBP4 are
presented in complex with the substances carvacrol and geranyl- acetone whose
repellent activity has been proved. The structural study of the complexes,
apart from the identification of the binding center and the protein residues
which participate in the recognition, provides additional information about the
chemical nature of affinity between ligands and protein, thus explaining the
observed difference of affinity among compounds with variable structural
characteristics. In conclusion, the structural study of complexes may
contribute to the development and/or the design of new repellents with improved
properties.
Additionally, kinetic studies of the enzyme GP were conducted in the presence
of flavonoids chrysin and flavopiridol, aiming at defining the difference in
binding affinity. Flavonoids are a category of natural lead compounds which
could be used in the design of potential hypoglycemic analogues. Kinetic
studies showed that this class of compounds binds at the allosteric inhibitor
site of the enzyme, in agreement with previous crystallographic studies,
whereas flavopiridol presents higher binding affinity than chrysin, probably
owing to its different structure.
Keywords:
OBP4, insect-repellent, malaria, glycogen phosphorylase(GP), flavonoids
