Are there any enzymes that force one or more of their substrates to travel a relatively long distance through a small opening/tube through the enzyme and to the active site? (not a transport protein)


First of all, as you mentioned, there are a lot of membrane / transport proteins with very nice, well defined tunnels. But you're looking for a soluble / cytosolic enzyme.

Some oxygen-dependent enzymes have quite long tunnels that oxygen is using. For example this one: http://www.jbc.org/content/283/36/24738.short or this one: http://europepmc.org/articles/PMC2698890

Then there are some enzyme with just deep active sites, I think the p450 BM3 is quite known for that, but any enzyme with a reasonable specificity (and especially those that have very reactive cofactors) will have a "tunnel".

You can also find long "tunnels" in enzymes that accept long substrates. I like this example of squalene synthase: http://science.sciencemag.org/content/277/5333/1811.full. The substrate first has to go deep into the enzyme to find the proton it needs to start a quite interesting reaction.

If you want to find new tunnels in your enzyme there are also tools available, such as CAVER: http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1002708 If you look at the papers citing this tool you might also find some cavities.

  • $\begingroup$ According to information on the CAVER website: The access tunnel is sometimes described as a "keyhole" in which analogy the lock is the enzyme and the substrate is the key that goes through the keyhole to the active site. The tunnels are commonly found in all six enzyme groups: Oxidoreductases,Transferases, Hydrolases, Lyases, Isomerases, and Ligases. Source: youtu.be/M6bW8lcM9jk $\endgroup$ – Dale Oct 6 '16 at 16:56
  • $\begingroup$ europepmc.org/articles/PMC2698890/figure/F2 $\endgroup$ – Dale Oct 6 '16 at 17:17
  • $\begingroup$ Other tunnel finding softwares include: (Mole, MolAxis, Hollow, etc.). ncbi.nlm.nih.gov/pmc/articles/PMC3341237 $\endgroup$ – Dale Oct 14 '16 at 21:35

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