Rossmann nucleotide-binding

Enzymes belonging to Class I function as monomers or homodimers (q 2). Their active sites contain a Rossmann nucleotide binding fold, also observed in dehydrogenases and other nucleotide-binding proteins. This fold consists of an alternating pattern of )8-strands and a-helices. The nucleotide binding fold is split into two halves, with a variable-length polypeptide insertion known as CPI be-... 

The AdoMet binding motif is similar to the Rossmann fold, which is well known from the nucleotide binding proteins [22]. It has been shown that the known crystal structures of methyltransferases are strikingly similar in the AdoMet-binding regions [23], which indicates that all AdoMet-utilizing enzymes may share a common divergent evolution. 

RGURE 13-16 The nucleotide binding domain of the enzyme lactate dehydrogenase, (a) The Rossmann fold is a structural motif found in the NAD-binding site of many dehydrogenases It consists of a six-stranded parallel /3 sheet and four a helices inspection reveals the arrangement to be a pair of structurally similar motifs... 

Figure 2-27 Topologies of the folds of three families of nucleotide binding oc/p proteins. Cylinders represent a helices and arrows p strands. (A) The ATPase fold for the clathrin-uncoating ATPase (B) The G-protein fold that hinds GTP and is found in ras proteins (C) The Rossmann fold that hinds NAD in several dehydrogenases. From Branden.262...

Rocky Mountain spotted fever 7 Rods (visual receptor cells) 390 Root hairs, dimensions of 30 Roseoflavin 788, 789s Rossmann fold. See Nucleotide-binding domain Rotamases 488 Rotary diffusion constant 463 Rotation of molecules 462,463 Rotational barrier 44 Rotifers 24, 25... 

MG Rossmann, D Moras, KW Olsen. Chemical and biological evolution of a nucleotide-binding protein. Nature 250 194-199, 1974. 

Despite sharing only 25% sequence identity, structural analysis indicates that both proteins of E. coli NADP-IDH and T. thermophilus NAD-IMDH are homodimers which share a common protein fold that lacks the p p p motif characteristic of the nucleotide binding Rossmann fold [23], The strict and distinct specificities of these enzymes provide an attractive model system for engineering specificity, while the extensive knowledge of substrate and coenzyme binding and catalysis provide the sound foundation critical for rational design. 

E. coli NADP-IDH and the homologous T. thermophilus NAD-IMDH have similar nucleotide-binding pockets that are quite distinct from the Rossmann fold found in many other dehydrogenases [16,17,22,23]. The pocket is constructed from three loops and an a-helix in IDH, the latter being substituted by a p-tum in IMDH (Fig. 1). Calculated as the ratio of kaJKm the E. coli NADP-IDH is 7000-fold more active with NADP than with NAD [1], whereas IMDH exhibits a 100-fold preference for NAD. 

Reitzer et al., 1999) and a MeCbl-binding fragment of E. coli methionine synthase (Drennan et al., 1994), the cofactor is sandwiched between two domains (Figure 8). The conserved domain possesses an a/ 3 structure reminiscent of the Rossmann fold of nucleotide-binding proteins (Rossmann et al., 1974) and consists of a twisted )-sheet of five parallel strands encased by five a-helices. It binds the lower, a-face of the corrin macrocycle and the substituents projecting idowni from this face, notably the dimethylbenz-imidazole ribofuranosyl nucleotide loop. 

These data established that each subunit of AtCAD5 was composed of two distinct domains comprising the Rossmann fold with the nucleotide-binding domain (residues 163-301) and catalytic domain (residues 1-162... 

The crystal structure of the enzyme (at 2.0 A resolution) consists of a single domain of eight a-helices and seven P-strands (PDB file 1VID) [45]. The fourth to eighth a-helices and the first five P-strands provide a nucleotide-binding motif (the Rossmann fold) to bind the adenine of the cofactor [46]. The reported crystal structure contains the enzyme, the coenzyme 5-adenosyImethionine, a magnesium ion, and a competitive inhibitor 3,S-dinitrocatechoI [45]. 

Rossmann, M.G. Moras, D. Olsen, K.W. Chemical and Biological Evolution of i Nucleotide Binding Protein . Nature 1974,250, 194-199. 

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