Last modified 19th April '95 © Birkbeck College 1995

Examples of Multimeric Enzymes

Dehydrogenases

Various dehydrogenases have been introduced in the section on enzymes in the chapter on tertiary structure .

Alcohol Dehydrogenase

Lactate Dehydrogenase

This is a tetrameric enzyme. In certain species there are two forms of the subunit, H and M, which results in a family of different isozymes. In heart muscle, the H4 form predominates, while M4 is the major form in skeletal muscle. Even though the two chains are significantly different, the MH3, M2H2 and M3H forms are found in the expected quantities, as the interface regions of both types are similar.

Consider how many distinct forms of M2H2 are possible.

The catalytic function does not involve interactions between the subunits, as the kinetic behaviour of, for example, the H3M form is the same as a 3:1 mixture of H4 and M4.

Examine the monomer .

This diagram shows the four subunits.

Here is the tetramer of the M4 isozyme, courtesy of BROOKHAVEN.

Glyceraldehyde 3-Phosphate Dehydrogenase

Note the similarity between this enzyme and lactate dehydrogenase:

Here is the complete tetramer .

Triose Phosphate Isomerase

The alpha/beta barrel structure of this enzyme has been described in the previous chapter . Here is a diagram .

Like many other structures of this fold, such as some of the glycolytic enzymes , this enzyme is dimeric. Here are two diagrams indicating the symmetrical arrangement of the 2 subunits and the relative orientations of the 2 barrel axes . Examine the crystal structure .

Glutamine Synthetase

The biologically active form of this enzyme is a dodecamer. The structure consists of two hexagonal rings, with an aqueous channel through the middle, stacked against each other.

Click here for a diagram of a single chain, courtesy of The Swiss-3DImage Collection , who also provide several further views of the dodecamer ; and also detail of the active site . Here is the crystal structure .

References

Abad-Zapatero, C., Griffith, J.P., Sussman, J.L. and Rossmann, M.G. (1987) Refined crystal structure of dogfish M4 apo-lactate dehydrogenase, J. Mol. Biol. 198, 445
Banner, D.W., Bloomer, A.C., Petsko, G.A., Phillips, D.C. and Wilson, I.A. (1976) Atomic coordinates for triose phosphate isomerase from chicken muscle, Biochem. Biophys. Res. Comm. 72, 146
Eklund, H., Samama, J.-P., Wallen, L., Branden, C.-I., Akeson, A. and Jones, T.A. (1981) Structure of triclinic ternary complex of horse liver alcohol dehydrogenase at 2.9Å resolution, J. Mol. Biol. 146, 561
Fersht, A.R. (1985) Enzyme Structure and Mechanism, W.H. Freeman & Co., New York, pp. 390-404
Skarzynski, T., Moody, P.C.E. and Wonacott, A.J. (1987) Structure of holo-glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus at 1.8Å resolution, J. Mol. Biol. 193 ,171
Yamashita, M.M., Almassy, R.J., Janson, C.A., Cascio, D. and Eisenberg, D. (1989) Refined atomic model of glutamine synthetase at 3.5Å resolution J. Biol. Chem. 264, 17681

As always, don't forget that there are numerous references cited within the Protein Data Bank files which are pointed to by the hypertext.

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J. Walshaw