New sequence motifs in flavoproteins: Evidence for common ancestry and tools to predict structure
✍ Scribed by Olivier Vallon
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 610 KB
- Volume
- 38
- Category
- Article
- ISSN
- 0887-3585
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✦ Synopsis
We describe two new sequence motifs, present in several families of flavoproteins. The ''GG motif'' (RxGGRxxS/T) is found shortly after the ␣dinucleotide-binding motif (DBM) in L-amino acid oxidases, achacin and aplysianin-A, monoamine oxidases, corticosteroid-binding proteins, and tryptophan 2-monooxygenases. Other disperse sequence similarities between these families suggest a common origin. A GG motif is also found in protoporphyrinogen oxidase and carotenoid desaturases and, reduced to the central GG doublet, in the THI4 protein, dTDP-4-dehydrorhamnose reductase, soluble fumarate reductase, steroid dehydrogenases, Rab GDP-dissociation inhibitor, and in most flavoproteins with two dinucleotide-binding domains (glutathione reductase, glutamate synthase, flavincontaining monooxygenase, trimethylamine dehydrogenase . . . ). In the latter families, an ''ATG motif'' (oxhhhATG) is found in both the FAD-and NAD(P)H-binding domains, forming the fourth -strand of the Rossman fold and the connecting loop. On the basis of these and previously described motifs, we present a classification of dinucleotidebinding proteins that could also serve as an evolutionary scheme. Like the DBM, the ATG motif appears to predate the divergence of NAD(P)H-and FAD-binding proteins. We propose that flavoproteins have evolved from a well-differentiated NAD(P)H-binding protein. The bulk of the substratebinding domain was formed by an insertion after the fourth -strand, either of a closely related NAD(P)H-binding domain or of a domain of completely different origin.