TAILIEUCHUNG - Báo cáo khoa học: Short-chain dehydrogenases/reductases (SDRs) Coenzyme-based functional assignments in completed genomes

Short-chaindehydrogenases/reductases (SDRs) are enzymes of great functional diversity. Even at sequence identities of typically only 15–30%, specific sequence motifs are detect-able, reflecting common folding patterns. We have devel-oped a functional assignment scheme based on these motifs and we find five families. Two of these families were known previously and are called classical and extended families, but they are now distinguished at a further level based on coenzyme specificities. | Eur. J. Biochem. 269 4409-4417 2002 FEBS 2002 doi Short-chain dehydrogenases reductases SDRs Coenzyme-based functional assignments in completed genomes Yvonne Kallberg1 2 Udo Oppermann1 Hans Jornvall1 and Bengt Persson1 2 1 Department of Medical Biochemistry and Biophysics and 2Stockholm Bioinformatics Centre Karolinska Institutet Sweden Short-chain dehydrogenases reductases SDRs are enzymes of great functional diversity. Even at sequence identities of typically only 15-30 specific sequence motifs are detectable reflecting common folding patterns. We have developed a functional assignment scheme based on these motifs and we find five families. Two of these families were known previously and are called classical and extended families but they are now distinguished at a further level based on coenzyme specificities. This analysis gives seven subfamilies of classical SDRs and three subfamilies of extended SDRs. We find that NADP H is the preferred coenzyme among most classical SDRs while NAD H is that preferred among most extended SDRs. Three families are novel entities denoted intermediate divergent and complex encompassing short-chain alcohol dehydrogenases enoyl reductases and multifunctional enzymes respectively. The assignment scheme was applied to the genomes of human mouse Drosophila melanogaster Caenorhabditis elegans Arabidopsis thaliana and Saccharomyces cerevisiae. In the animal genomes the extended SDRs amount to around one quarter or less of the total number of SDRs while in the A. thaliam and S. cerevisie genomes the extended members constitute about 40 of the SDR forms. The numbers of NAD H -dependent and NADP H -dependent SDRs are similar in human mouse and plant while the proportions of NAD H -dependent enzymes are much lower in fruit fly worm and yeast. We show that in spite of the great diversity of the SDR superfamily the primary structure alone can be used for functional assignments and for predictions of coenzyme

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