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I'm reading about protein folding on Wikipedia and I stumbled on a bit about a class of proteins called chaperones that aid in the folding of proteins by:

...reducing possible unwanted aggregations of the polypeptide chain that might otherwise slow down the search for the proper intermediate...

However, they aren't considered to be catalysts because they do not actually speed up the folding process. My thought is that without these chaperones, the polypeptides chain would go through a long process of finding a proper intermediate and therefore should be considered catalysts.

Where am I going wrong in my thinking?

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    $\begingroup$ Without these chaperones, the polypeptide chain would end up folded in a wrong way or not folded at all. Then again, who said they are not considered to be catalysts? $\endgroup$ – Ivan Neretin Aug 9 '17 at 5:10
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    $\begingroup$ The usual definition of catalyst is that it has to take part in the reaction. The reaction is usually of zeroth order kinetic, regarding the catalyst. Here it sounds like those chaperones are inhibiting an unwanted side reaction. That could possibly lead to catalyst-like kinetics. Any way, catalyst is just a name. $\endgroup$ – Karl Aug 9 '17 at 8:03
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I don’t think you are wrong. Actually molecular chaperones have been named enzymes in some texts. The molecular chaperones comprise several unrelated classes of proteins that have rather different functions.

Most molecular chaperones are ATPases (enzymes that catalyze ATP hydrolysis), which bind to unfolded polypeptides and apply the free energy of ATP hydrolysis to effect their release in a favourable manner.

It is also made evident in the way some of them function (they possess some ATPase activity), it suggests they’re kind of catalysts enzymes:

They function in an ATP-driven process to reverse the denaturation and aggregation of proteins (processes that are accelerated at elevated temperatures), to facilitate the proper folding of newly synthesized polypeptides as they emerge from the ribosome, to unfold proteins in preparation for their transport through membranes.

Two classes of molecular chaperones have been well studied. Both are found in organisms ranging from bacteria to humans.

  1. The heat shock proteins 70 (Hsp70)

The first class is a family of proteins called Hsp70. They function in an ATP-driven process to reverse the denaturation and aggregation of proteins (processes that are accelerated at elevated temperatures), to facilitate the proper folding of newly synthesized polypeptides as they emerge from the ribosome, to unfold proteins in preparation for their transport through membranes and to subsequently help them refold.

  1. Chaperonins

Are also heat shock proteins that form large, multisubunit, cagelike assemblies that are universal components of prokaryotes and eukaryotes. They bind improperly folded globular proteins via their exposed hydrophobic surfaces and then, in an ATP-driven process, induce the protein to fold while enveloping it in an internal cavity, thereby protecting the folding protein from nonspecific aggregation with other unfolded proteins.

Other chaperones e.g. Hsp90 proteins (have a regulatory role in that they induce conformational changes in nativelike substrate proteins that result in their activation or stabilization) and Trigger factor (prevents the intra- and intermolecular aggregation of newly synthesized polypeptides as they emerge from the ribosome by shielding their hydrophobic segments) However, unlike most other chaperones, trigger factor does not bind ATP.

Enzymes are more or less catalysts in biological systems, so yes its right to synonimise them with catalysts.

References

  1. Biochemistry (Voet and Voet) Section 9.2 Folding Accessory Proteins, Molecular Chaperones: The GroEL/ES System.

  2. Lehninger Principle of Biochemistry Chapter 4, Protein Denaturation and Folding.

  3. Biochemistry R. Garret, C. Grisham. Chapter 31 Completing the Protein Life Cycle: Folding, Processing, and Degradation

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There are quite a few reasons why one would say that chaperones are not catalysts. For one, they only assist by shielding away unwanted influences. They don’t really actively assist in folding a protein — if you have an image of a chaperone perfoming some kind of origami, that is inaccurate to the best of my knowledge.

Therefore also, folding is not necessarily faster, it only has a greater success rate. According to the currently accepted thermodynamic model (again to the best of my knowledge), the folded protein is a pretty significant local minimum of the potential energy field so that if no extremely wrong paths are taken the correct structure should result.

The most important reason, however, is that folding is simply not a chemical reaction that could be catalysed. It is merely a physical process like rotation, no bonds are formed or broken in the process. (Hydrogen bonds don’t count.) If there is no reaction, then whatever assists or speeds up cannot be considered a catalyst.

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    $\begingroup$ Your last paragraph isn't true. en.wikipedia.org/wiki/Topoisomerase $\endgroup$ – Mithoron Aug 9 '17 at 16:13
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    $\begingroup$ Rest pretty much too. en.wikipedia.org/wiki/Chaperone_(protein) You should have checked sources :( Afinsen made rather a "guideline" ;) $\endgroup$ – Mithoron Aug 9 '17 at 16:26
  • $\begingroup$ @Mithoron What does topoisomerase have to do with it? An enzyme that breaks a phosphate backbone bond in DNA to assist in unwinding and then reforms it? Not only is that clearly a catalytic process but it also does not concern proteins. $\endgroup$ – Jan Aug 10 '17 at 0:24
  • $\begingroup$ You are right about the rest, though. I didn’t check sources, I relied on my memory from the biochem classes back at uni some eight years or so ago O:-) $\endgroup$ – Jan Aug 10 '17 at 0:27
  • $\begingroup$ Topoisomerases aren't best example but difference in product and substrate does lie only in intermolecular interactions likewise in proteins. Second link covers it though, stating that some chaperones do catalyse, even use up ATP for it. Also h-bonds in proteins definitely do count ;) $\endgroup$ – Mithoron Aug 10 '17 at 0:38

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