Dehydrogenases quaternary structure

FIGURE 6.41 The quaternary structure of liver alcohol dehydrogenase. Within each subunit is a six-stranded parallel sheet. Between the two subunits is a two-stranded antiparallel sheet. The point in the center is a C9 symmetry axis. (Jane Richardson)... 

Packman, L.C., and Perham, R.N. (1982) Quaternary structure of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus studied by a new reversible cross-linking procedure with bis(imidoesters). Biochemistry 21, 5171-5175. 

Figure 8.10 The quaternary structure of proteins. The enzyme lactate dehydrogenase (EC 1.1.1.27) has a relative molecular mass of approximately 140 000 and occurs as a tetramer produced by the association of two different globular proteins (A and B), a characteristic that results in five different hybrid forms of the active enzyme. The A and B peptides are enzymically inactive and are often indicated by M (muscle) and H (heart). The A4 tetramer predominates in skeletal muscle while the B4 form predominates in heart muscle but all tissues show most types in varying amounts.

B is lactate dehydrogenase (Chapter 15). The plant agglutinin concanavalin A has a quaternary structure resembling that in Fig. 7-11C. -----------... 

The term "quaternary structure" refers to the interaction of several polypeptide chains in a noncovalent manner to form multisubunit protein particles termed oligomers. Individual subunit polypeptide chains are also referred to as protomers. Oligomers usually have an even number of subunits (two or more). The noncovalent interactions may be of the hydrophobic, hydrogen bond, or the polar type. Examples are hemoglobin and lactate dehydrogenase (four protomers each) and many allosteric enzymes. 

Electrospray ionization has allowed the observation of a great number of non-covalent complexes protein-protein, protein-metal ion, protein-drug and protein-nucleic acid. About one-third of the proteins exist as multimeric forms. Mass spectrometry allows the study of their quaternary structure. This has been done for alcohol dehydrogenase (ADH) from horse liver and from yeast. The ESI spectra are displayed in Figure 8.22. The horse liver ADH is observed to be dimeric whereas that of yeast is tetrameric [131]. 

Figure 9.10. The quaternary structure of glutamate dehydrogenase reveals a complex array of subunit interfaces. See color insert.

Fig. 1. Position of the two similar mononucleotide binding domains, Ai and Aj, comprising together the NAD binding region, within the single polypeptide chains of four different dehydrogenases. The catalytic domains, C, of LDH and s-MDH are similar in structure, but different to the catalytic domains D and E in LADH and F in GAPDH. The primary function of the amino terminal arm domain, B, in LDH is to stabilize the quaternary structure.

A review of the known sequences of each of the dehydrogenases has been given in the appropriate chapters of this volume. Table III shows the available sequence information in relation to the known tertiary and quaternary structures (4,5,W-18,S0a-d,43). 

The differences in quaternary structure as opposed to the preservation of tertiary structure of the NAD+ binding domains suggest that subunit associations are of more recent origin (9). Buehner et al. 17) used the preservation of the Q axis in GAPDH, LDH, and s-MDH, and the close resemblance of the dimer of s-MDH to one-half of the LDH molecule, to suggest an evolutionary tree (Fig. 12). Also included in Fig. 12 is the relationship of an FMN mononucleotide binding unit in flavodoxin 24) to the dehydrogenases. 

The data cited thus far indicate that both alkaline phosphatase and liver alcohol dehydrogenase contain heterogeneous populations of metal atoms of the same species. In both instances, only two of the zinc atoms native to the enzyme appear to be involved in enzymatic activity. The remaining metal atoms do not have a catalytic role but appear to influence the quaternary structure of the protein, although the details of the manner in which this is accomplished are as yet uncertain. These observations have induced us to reexamine the possible effects of metals on structure in other proteins, including those having only single chains. 

Probably the most fully studied group of isoenzymes is that of lactate dehydrogenase (LDH). The quaternary structure of the enzyme consists of four subunits that are of two different types. One is labeled H because it is the predominant subunit present in the LDH enzyme found in heart muscle cells. The other, labeled M, predominates in other muscle cells. There are five possible ways to combine these four subunits to form the enzyme (see I Figure 10.14). Each combination has slightly different properties, which allows them to be separated and identified by elecfrophoresis. 

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