Monday, October 01, 2007

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 kcat and KM 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.

5 comments :

  1. These catalytically perfect enzymes fascinate me. I can't even imagine an enzyme processing hundreds of thousand of molecules of superoxide per second.

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  2. Hi Larry,

    Can I make a slight correction? Your lead here made me think that PhilipJ had written about superoxide dismutase, and happened to illustrate it within one of David Goodsell's images. But PhilipJ is just quoting some of the text written by David Goodsell himself in the current Molecule of the Month entry on the PDB (virtually all of these entries are written and illustrated by David).

    As a side note, David Goodsell--while a brilliant pen-and-ink illustrator and watercolourist--creates most of the Molecule of the Month images using software he developed himself that derives those lovely pen-like lines from the z-buffer of molecular model.

    Love this blog... keep up the good work...

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  3. I co-taught a class in symbiosis where we talked about superoxide dismutase. Zooxanthellate cnidaria (corals, anemones and zoanthids) have high concentrations of this enzyme in tissue close to the photosynthetic zooxanthellae. Concentration drops off as you move farther from zooxanthellae-inhabiting tissue. These cnidarians have adapted to the high oxygen and free radical concentrations produced in their tissues by photosynthesis by producing high quantities of SOD.

    When you bring up its speed, its makes a lot more sense. I need to go back to the literature but maybe researchers were measuring activity instead of concentration. I always thought that concentration was high near the algae dropping off as you move farther away. But perhaps the enzyme is more active near the algal cells to cope with high rates of photosynthesis.

    Anyways, thanks for the knowledge! I'll be sure to mention SOD's speed if we teach it again next spring.

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  4. Matt says,

    These catalytically perfect enzymes fascinate me.

    Oh, oh. You've touched another nerve—I have lots of them.

    We've eliminated the word "perfect" from our description of these enzymes and I've tried to get all other textbooks to do the same.

    The reason is that there are many enzymes where the ideal rate may have to be less than the theoretical maximum. In those cases, natural selection may have favored a slowing down of the enzyme. Thus, the "perfect" enzyme in a biological sense is one where the reaction rate is compatible with everything else that's going on in the cell.

    I realize that you said "catalytically perfect" but even that is going too far, in my opinion. It's better to avoid the word "perfect" altogether since it carries so much baggage.

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  5. Nicholas,

    Thanks for the insight. I had no idea that Goodell's molecule drawings were, in part, computer generated. It makes a lot of sense, but I just didn't think about it.

    In our textbooks we made a deliberate attempt to have only two kinds of structure figures.

    One kind are those that show computer-generated structures that the students can reproduce on their own computers. We give them the PDB references.

    The other kinds are cartoons that make no great effort to show the actual structure. They're used when we want to simplify the explanation. We call those figures "jelleybeans" because they often resemble colored jellleybeans. Here's an example [Transcription of the 7SL Gene].

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