Proteopedia: Rossmann fold: A beta‐alpha‐beta fold at dinucleotide binding sites

Abstract

The Rossmann fold is one of the most common and widely distributed super-secondary structures. It is composed of a series of alternating beta strand (b) and alpha helical (a) segments wherein the b-strands are hydrogen bonded forming a b-sheet. The initial beta-alpha-beta (bab) fold is the most conserved segment of Rossmann folds. As this segment is in contact with the ADP portion of dinucleotides such as FAD, NAD, and NADP it is also called as an "ADPbinding bab fold". The Proteopedia entry on the Rossmann fold (Available at: http://proteopedia.org/w/Rossmann_fold) was generated to illustrate several structural aspects of super families of FAD and NAD(P) binding proteins: (1) The coenzymes FAD and NAD(P) share the basic adenosine diphosphate (ADP) structure. (2) The bab fold motif that is common to both FAD and NAD(P) binding enzymes accommodates the common ADP component of these two coenzymes. (3) In both FAD and NAD(P) binding sites, the tight turn between the first b-strand and the a-helix is in contact with the two phosphate groups of ADP. (4) Keywords: protein structure function and folding; enzymes and catalysis; protein design; biochemical evolution; molecular graphics and representations; comparative biochemistryIn a very large superfamily of dinucleotide binding enzymes, the domains that bind a dinucleotide such as FAD, NAD, and NADP share a common super-secondary structure that is partly composed of a series of alternating beta strand (b) and alpha helical (a) segments wherein the b-strands are hydrogen bonded forming a central b-sheet with helices on either side. There can be up seven strands in one sheet. This domain structure was named "Rossmann fold" after Michael G. Rossmann who first reported it as a common structure in a variety of nucleotide binding proteins, such as lactate dehydrogenase and flavodoxin [1].The Rossmann fold is one of the five most common structural motifs that appear in a myriad of proteins [2,3]. The most widely distributed protein folding motifs are thought to be remnants of most ancient protein architectures [2,3]. In many textbooks, the Rossmann fold is defined as a babab structure in accordance with the original report [1]. However, elucidation of the structures of many dinucleotide binding enzymes revealed a great diversity in the overall structure of the dinucleotide binding domains. The major differences among dinucleotide binding domains of proteins include extensive divergence of the primary structure, variable number of b-strands in the complete b-sheet that forms the Rossmann fold, and large variations in the length and secondary structure of the segment that connects the second and third b-strands.The diversity of the Rossmann fold can be illustrated by two enzymes as examples. In dogfish lactate dehydrogenase the NAD binding motif, babab fold, is a continuous 60 residues long segment (PDB ID: 3LDH) [4]. In contrast, in yeast D-amino acid oxidase, the FAD binding domain includes only the initial bab fold in a continuous segment of 30 residues, but betwee...

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