Importance of conformational changes during catalysis

[bard]

Hi everyone, my teacher talked about the importance of conformational changes during catalysis. But I don't understand the importance of the changes. Can someone help me understand?

 

[GoneRogue]

It's been a while since I've taken bio, but maybe I can help you out. A conformational change is a structural change in the active site (where the substrate binds) on the enzyme. The cause of the conformational change, in the case of an allosteric enzyme, happens when the allosteric activator binds to the allosteric site on the enzyme. To sum it up, the conformational change in the case of an allosteric enzyme allows substrate to bind to the active site.

 

[Moonbear]

GoneRogue has provided a good start to the answer. Conformational changes are not only a change at the active site, but they occur upon substrate binding to the active site. The change in conformation of the enzyme due to the presence of the substrate is believed to result in a release of energy that then lowers the free energy of activation of the reaction.

If you're up to the challenge, here's a reference and abstract for a relatively recent review article that discusses this (I'm not sure if you'll have access to the journal, but if you're not sure, your library can help).

Curr Opin Struct Biol. 2003 Apr;13(2):184-92.
Catalysis by enzyme conformational change as illustrated by orotidine 5'-monophosphate decarboxylase.
Gao J.

An energy decomposition scheme has been used to elucidate the importance of the changes of enzyme conformational substates to the reduction of the activation barrier in enzyme-catalyzed reactions. This analysis may be illustrated by the reaction of orotidine 5'-monophosphate decarboxylase, which exhibits a remarkable rate enhancement of over 17 orders of magnitude compared to the uncatalyzed process. The mechanism shows that the enzyme conformation is more distorted in the reactant state than in the transition state. The energy released from protein conformation relaxation provides the predominant contribution to the rate enhancement of orotidine 5'-monophosphate decarboxylase. The proposed mechanism is consistent with results from site-directed mutagenesis experiments, in which mutations distant from the reactive center can have significant effects on the catalytic rate enhancement (k(cat)), but rather a small influence on the binding affinity for the substrate (K(M)).

 

[DocToxyn]

I realize this post is specifically about catalytic processes but I would like to add that a conformational change, while commonly associated with enzymes and their activity, also takes place in the function of other proteins such as those which move substances across the plasma membrane, e.g. NMDA channel, voltage-gated calcium channels, or dopamine transporter (DAT). In the case of the DAT, this Na+/Cl- dependent symporter transports the neurotransmitter dopamine from the synapse back into the nerve terminal as a means of termination of signal transduction. To do so the protein carrier is found in a state where the high-affinity binding site for dopamine is exposed to the extracellular space and upon dopamine binding the protein undergoes a conformational change to move the dopamine back into the nerve terminal and allow for its repackaging into synaptic vesicles for a later release event. This transporter and its activity also plays a significant role in the effects of cocaine and certain other drugs of abuse, thus one reason for our interest in this protein.

Check- Aspartate 345 of the dopamine transporter is critical for conformational changes in substrate translocation and cocaine binding. for a current example of how this conformational change is being studied.

 

[Moonbear]

DocToxyn is right to point out that conformational changes are not restricted to catalytic reactions. Indeed, it's well worth noting that conformational changes of molecules is a common theme in the function of many biological processes.

Recognizing that conformational changes, even of just a small part of a molecule, can have rather large effects on the ability of that molecule to interact with other molecules will help understand many biological processes.

 

[kalladin]

If we assume the lock and key theory for all biological catalysts, then a conformational change in the enzyme/hormone/nucleotide/etc. would allow the entering and binding of the "key" (substrate). This is one of the main reasons why enzymes show such high substrate specificity. Also, when there is a conformation change, it allows the formation of a transistion state complex with the substrate, which once formed (if I'm not mistaken), ensures that the enzymatic reaction completes and produces a product.

The function of a protein is highly, if not ultimately influenced by its conformation. Certain active amino acids in the active site of the protein must be put close together by folding of the protein so that they can simultaneously act on the substrate that is to be modified.

K.