Dehydrogenases binding domains

Ohlsson, I., Nordstrom, B., Branden, C.-I. Structural and functional similarities within the coenzyme binding domains of dehydrogenases. /. Mol. Biol. 89 339-354, 1974. 

H8. Hirono, A., Kuhl, W., Gelbart, T., Forman, L., Fairbanks, V. F., and Beutler, E., Identification of the binding domain for NADP of human glucose-6-phosphate dehydrogenase by sequence analysis of mutants. Proc. Natl. Acad. Sci. U.S.A. 86,10015-10017 (1989). 

Figure 4.9 (a) Triose phosphate isomerase (TIM), has a (3-a-(3 structure made up of eight P-a motifs terminating in a final a-helix, which form a barrel-like structure, (b) An open twisted P-sheet with helices on both sides, such as the coenzyme-binding domain of many dehydrogenases. (From Branden and Tooze, 1991. Reproduced by permission of Garland Publishing, Inc.)... 

Several lines of evidence—sequence analysis, mutagenesis studies, and the solved 3D structure of homologs of 11P-HSD—indicate that the nucleotide binding site in these enzymes has many similarities to that in other classes of dehydrogenases. For many dehydrogenases, the nucleotide binding domain... 

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 2-13 (A) Stereoscopic view of the nucleotide binding domain of glyceraldehyde phosphate dehydrogenase. The enzyme is from Bacillus stearothermophilus but is homologous to the enzyme from animal sources. Residues are numbered 0-148. In this wire model all of the main chain C, O, and N atoms are shown but side chains have been omitted. The large central twisted P sheet, with strands roughly perpendicular to the page, is seen clearly hydrogen bonds are indicated by dashed lines. Helices are visible on both sides of the sheet. The coenzyme NAD+ is bound at the end of the P sheet toward the viewer. Note that the two phosphate groups in the center of the NAD+ are H-bonded to the N terminus of the helix beginning with RIO. From Skarzynski et al.llla (B) Structural formula for NAD+.

A crystal structure of a ternary complex of horse liver alcohol dehydrogenase with NADH and the inhibitor, dimethyl sulfoxide, first at 4.5 A resolution1365 and a further refinement to 2.9 A resolution,1366 has been published by Eklund et al. The gross structure of the ternary complex is similar to that of the free enzyme structure. Each subunit is divided into a coenzyme-binding domain and a catalytic domain. The subunits are joined together near the... 

The structures of several dehydrogenases have now been solved. The work on these has been reviewed in depth in the literature, as have their physical and kinetic properties.1,9,10 Some generalizations can be made. As was discussed in Chapter 1, section D6, the subunits may be divided into two domains a catalytic domain, which can be quite variable in structure, and a nucleotide-binding domain, which is formed from a similar overall folding of the polypeptide chain for all the dehydrogenases. The detailed geometry of the nucleotide-binding... 

Certain combinations of secondary superstructures are often found in proteins and control their structure and function. The most frequent is the /fayS-unit, where an a-helix bridges two /1-strands. This is the prevailing feature in most coenzyme-binding domains of dehydrogenases [7]. Other important superstructures include a,a-dimers, /1-meanders and //-barrels. 

A domain is an independently folded region of a protein e.g., the NAD+-binding domain of glyceraldehyde-3-phosphate dehydrogenase. 

Fig. 33. Diagram illustrating the arrangement of strands and helices in the NAD-binding domain of dehydrogenases. (B designed by B. Furugren.) From the work of Branden and colleagues [72],...

---