Superoxide Dismutase Is a Really Fast Enzyme

PhilipJ has posted the latest "Molecule of the Month" on Biocurious [Molecule of the Month: Superoxide Dismutase]. The molecule is superoxide dismutase from cow (Bos taurus) drawn by David Goodsell from the 2SOD (formerly 1SOD) structure in the Protein Data Bank. This structure is from 1980.

The formal name of this enzyme is copper-zinc superoxide dismutase in order to distinguish it from other, unrelated, superoxide dismutases. As noted on the Biocurious website, the main reason for having this enzyme is to get rid of dangerous free radical forms of oxygen that are produced in a number of cellular reactions; notably, membrane-associated electron transport and photosynthesis. (Superoxide dismutase is found in all species.)

The reaction involves a copper ion (Cu²⁺) at the active site of the enzyme (E). A free radical, such as the toxic superoxide radical anion, binds to the coper ion and an electron is transferred from the superoxide radical to the copper ion. This leads to the reduction of the copper ion from the +2 form to the +1 form as it picks up a single negative charge from the electron. In the second step, this electron is passed from the copper ion back to another superoxide anion which then combines with two protons to make hydrogen peroxide (H₂O₂). Hydrogen peroxide can be easily converted to water + molecular oxygen by ubiquitous catalase enzymes.


Superoxide dismutase is an important enzyme and it's role in scavenging free radicals would be more than enough to justify its inclusion in biochemistry textbooks. But there's another reason why this enzyme is discussed. It's one of the fastest enzymes known to biochemists as shown in the table below.



I suspect that most of you aren't familiar with the Michaelis-Menten constants k_cat and K_M but that doesn't matter. Trust me, these are very fast enzymes.

In fact, superoxide dismutase is faster than it has any right to be. The maximum rate of an enzymatic reaction was thought to be limited to the rate of diffusion inside the cell. This makes sense since the substrate (superoxide anion) has to collide with the active site copper ion before a reaction can occur. But measurements of the actual enzymatic rate gave a result that was faster than theoretically possible given the diffusion rates inside the cell.

It wasn't until the structure of the enzyme was solved that this mystery was cleared up. Look at the structure shown above. This is the human version of copper-zinc superoxide dismutase from 2003 [1HL5]. The structure is drawn in a way that highlights the charges on the surface of the enzyme. Red side chains are negatively charged and blue side chains are positively charged. The entry channel to the copper ion (green) at the active site is lined with positively charged amino acid residues. These suck in the negatively charged oxygen radicals like a vacuum cleaner and feed them to the active site. That's how the enzyme can operate so fast.