Quaternary Structure - Multimeric Enzymes
Index to Course Material
Index to Section 11
Alcohol Dehydrogenase
This page describes some further examples of multimeric enzymes (some others are
described in the overview of this Section. Enzymes are
biological catalysts, which mediate a vast number of reactions in the biochemical
pathways of life. Apart from some RNA molecules which have been relatively recently
shown to have catalytic activity (ribozymes), all enzymes are proteins. They
are highly specific in the reactions they catalyse, and bind their substrates
by non-bonded interactions (refer to the appropriate page in
Section 7 of the course). The catalytic
regions of the enzymes which bind the substrates are called active sites.
In some cases, oligomerization is a requisite for the existence of a complete
active site; make sure you have read the
overview of this Section, which describes two examples.
Some Dehydrogenases:
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 1ldm (260Kb) [Bbk|BNL|ExP|Waw|Hal].
This diagram shows the four subunits.
Here is the tetramer of the M4 isozyme, courtesy of
Brookhaven PDB.
Glyceraldehyde 3-Phosphate Dehydrogenase
Note the similarity between the arrangements of this enzyme and lactate dehydrogenase.
What type of symmetry is this? Make sure you can identify the axes of
symmetry.
In this case however, the
asymmetric unit of the crystal structure includes the complete tetramer
1gd1 (966Kb) [Bbk|BNL|ExP|Waw|Hal].
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
other glycolytic enzymes, this enzyme is dimeric. However, there is no
evidence for cooperativity of substrate binding during catalysis. 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 1tim (322Kb) [Bbk|BNL|ExP|Waw|Hal].
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 (the asymmetric unit is an entire dodecamer)
2gls (3.6Mb) [Bbk|BNL|ExP|Waw|Hal].
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.
Index to Course Material
Index to Section 11
Alcohol Dehydrogenase
Last updated 3rd Jul '96