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Functional Constraints of 6-Phosphogluconate Dehydrogenase (6-PGD) Based on Sequence and Structural Information

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Abstract

The pentose phosphate cycle is considered as a major source of NADPH and pentose needed for nucleic acid biosynthesis. 6-Phosphogluconate dehydrogenase (6PGD), an enzyme participating in this cycle, catalyzes the oxidative decarboxylation of 6PGD to ribulose 5-phosphate with the subsequent release of CO2 and the reduction of NADP. We have determined the amino acid sequence of 6PGD of Bactrocera oleae and constructed a three-dimensional model based on the homologous known sheep structure. In a comparative study of 6PGD sequences from numerous species, all the conserved and variable regions of the enzyme were analyzed and the regions of functional importance were localized, in an attempt promoted also by the direct involvement of the enzyme in various human diseases. Thus, analysis of amino acid variability of 37 6PGD sequences revealed that all regions important for the catalytic activity, such as those forming the substrate and coenzyme binding sites, are highly conserved in all species examined. Moreover, several amino acid residues responsible for substrate and coenzyme specificity were also found to be identical in all species examined. The higher percentage of protein divergence is observed at two regions that accumulate mutations, located at the distant parts of the two domains of the enzyme with respect to their interface. These peripheral regions of nonfunctional importance are highly variable and are predicted as antigenic, thus reflecting possible regions for antibody recognition. Furthermore, locating the differences between diptera 6PGD sequences on the three-dimensional model suggests probable positions of different amino acid residues appearing at B. oleae fast, intermediate, and slow allozymic variants.

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Authors and Affiliations

  1. Department of Genetics, Agricultural University of Athens, Iera Odos 75, Votanikos, 118 55, Athens, Greece

    George N. Goulielmos, Elias Eliopoulos, Michael Loukas & Spyros Tsakas

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  1. George N. Goulielmos
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  2. Elias Eliopoulos
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  3. Michael Loukas
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  4. Spyros Tsakas
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Correspondence to George N. Goulielmos.

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Abbreviations used: 6Pgd, 6-Phosphogluconate dehydrogenase gene; 6PGD, 6-Phosphogluconate dehydrogenase enzyme; NADPH, nicotinamide adenine dinucleotide phosphate; ADP, adenine dinucleotide phosphate; TNBS, 2,4,6 trinitrobenzensulfonic acid.

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Goulielmos, G.N., Eliopoulos, E., Loukas, M. et al. Functional Constraints of 6-Phosphogluconate Dehydrogenase (6-PGD) Based on Sequence and Structural Information. J Mol Evol 59, 358–371 (2004). https://doi.org/10.1007/s00239-004-2630-y

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