The pentose phosphate cycle is considered as a major Source or NADPH and pentose needed for nucleic acid biosynthesis. 6-Phosphogluconate dehydrogenase (6PGD), an enzyme participating in this cycle. catalyzes the oxidative decarboxylation or 6PG to ribulose 5-phosphate with the subsequent release of CO2, and the reduction of NADP. We have determined the genomic sequences of 6PGD of two species of Tephritidae, the medfly Ceratitis capitata and olive fruit fly Bactrocera oleae, and constructed a three-dimensional model of 6PGD of C capitata based on the homologous known sheep structure. In a comparative study of 6PGD sequences from seven species, all the conserved and variable sites of the enzyme were analyzed and the regions of functional importance were localized, an attempt promoted also by the direct involvement of the enzyme in various human diseases. The enzymes between the two species of Tephritidae have a very high homology and further examination of the variable positions with respect to the highly conserved binding site residues enabled their grouping in three distinct categories, with possible association to dimer formation, functional specificity.. and antigenicity. Moreover, placement of sequence differences on the 3-D model suggests probable sites accommodating variations appearing at the allozymic variants of both species. (c) 2006 Elsevier Inc. All rights reserved.