Morel et al. (2008)

Carbonic anhydrase is one of the most prevalent enzymes in living organisms and is responsible for catalyzing the reversible hydration of inorganic carbon. It is seen in both vertabrates, where it hydrates carbon dioxide into carbonic acid and plant life, where it converts carbonic acid into carbon dioxide in order to feed into photosynthesis. The enzyme’s discovery was made in the 1930s and since then it had been assumed zinc was the only cofactor that could activate this enzyme. In our discussion on Wednesday we will look at a cousin of carbonic anhydrase that uses another surprising cofactor to catalyze this all too important chemical reaction.

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8 Responses to “Morel et al. (2008)”

  1. Porter Marsh Says:

    In the active site structure section of the paper, the paper says there are 3 carefully positioned water molecules H bonding to each other. In addition to those three in the active site, it says there is a number of well ordered water molecules above the active site. Considering this enzyme was found in the ocean, how do Na+ or Cl- ions affect this water network? Does the enzyme have a way to exclude the ions from interfering with the H bond network? I feel like water in the presence of Na+ or Cl- would be more likely to be arranged around those instead of each other.

  2. Adam Settimo Says:

    Diatoms really seem to be very adaptive creatures. I remember looking at them in introductory bio and being told that they can be found in all water, fresh and marine, and soil. This makes me wonder if these Cd-CDCA1 enzymes are found in the fresh water or soil diatoms? I would imagine that the availability of rare metals varies among these environments, which makes me wonder if this is a method used by other diatoms.

    In this paper they talk about the metal center being attached by two water molecules, which are attached to a third through H bonding. The third is attached to many more water molecules well ordered above that. Later during the substrate binding site section there is talk about the 12 hydrophobic amino acids that surround the channel leading to the metal center. How do the water molecules described above interact with the hydrophobic amino acids of the channel?

  3. Tony Says:

    It is fascinating that such a rare metal would be employed by a biological organism. Also cadmium is a soft acid which is usually toxic to life. Why would diatoms use cadmium instead of zinc if zinc works better? Does sequestering cadmium for use help lower its toxicity? Also in the intro paper they mention cobalt can be employed too instead. I wonder how or why this would be the case.

  4. Kevin Greenwood Says:

    In the section on substrate binding, acetate (or an acetate-like group) is crucial to the functioning of this protein. It is mentioned that one of the active site molecules “is presumably deprotonated owing to Cd co-ordination” to form the nucleophile that attacks carbon dioxide. It is interesting that the acetate directly replaces the hydrogen-bonded water molecules in the CDCA1-R2 structure; I hadn’t considered that multiple water molecules could act as an isostere for acetate.

    The speculation on the hydrophobic channel is also interesting. Being less polar than the product, it should be able to move carbon dioxide into the channel and funnel it to the awaiting nucleophile. That brings up the question of how the product is ejected from the active site. If there is no room in the active site to hold the product, or there isn’t a conformational change in the enzyme to let it slip away, then the lipophilic residues could act to punt out the bicarbonate. With a 4 to 5 angstrom diameter, this is big enough to allow bicarbonate to pass through, and small enough that the nonpolar residues would have to interact with the product. The authors state that this channel might be the entry or escape route for the substrate. But based on the properties of this group, could it be used for both?

  5. Josh Ellsworth Says:

    I found it interesting that the enzyme cold adopt a stable metal free conformation, and that allowed for its cambialistic nature. Fun vocabulary word. Were any experiments done with other CA homologues and Cadmium? The paper mentioned that metal exchange rates are very slow with most CA enzymes, but the observation about the Glycine residues acting as hinges to stabilize the metal free conformation made me wonder what the results of site directed mutagenesis to Glycine on a human CA would be. On a more elementary note, what about zinc makes it the go to metal for CA? Is it the electron configuration?, abundance? Why do the CDCA enzymes scavenge Cadmium and not other ions of similar size, like Cu + or Mg 2+ ?

  6. Daniel Begay Says:

    Hearing about cadmium brings me back to CHM 350 and ‘cadmium cookies’.

    As we all know, cadmium is toxic and is more efficient as a catalyst for this enzyme. Does scarcity play a factor in its efficiency as a catalyst? I’m curious to see if other toxic metals are able to work as efficiently. Such as mercury, as it is abundant (slightly due to contamination) on the ocean floors, can it be used as a catalyst?

    Lastly, on the topic of substrate binding, it says that acetate was used but was also a weak inhibitor for beta-CA. Through the technique of using inhibitors, were they able to determine if this enzyme had multiple active sites or the type of inhibitor it is (competitive/noncompetitive)?

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