Biomolecules:
Enzymes
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In this module:

Introduction
Enzymes' Capabilities
Models of Enzyme Action
Enzyme Kinetics
Competitive Inhibition
Noncompetitive Inhibition
An Enzyme at Work
Protease Inhibitors
Ribozymes

Ribozymes

For many years, it was believed that the only enzymes were proteins and their cofactors. Recently, however, several RNA enzymes have been discovered. These enzymes are called ribozymes and exhibit all the same features (specificity, transition state stabilization, Michaelis Menten kinetics) as protein enzymes.

One group of ribozymes is known as hammerhead ribozymes. An example of a hammerhead ribozyme is shown at right. These ribozymes were originally discovered in viruses that use RNA to store their genetic information. These small RNA's were originally studied because they had the ability to cut themselves out of larger RNA molecules without the assistance of a protein enzyme. Later they were shown to be able to cleave other RNA molecules containing the NUX pattern of nucleotides (N represents any nucleotide, U represents uracil, and X can be adenine, uracil, or cytosine), making them true enzymes. In the structure at right, the phosphodiester bond between the ball-and-stick nucleotides is cleaved, assisted by the Mg2+ ion shown as a spacefilling sphere.

Click on the step numbers below to see the hammerhead ribozyme's mechanism. Click on the mouse at left to clear the images and text.

The hydrated Mg2+ ion has two functions, both mediated by its waters of hydration. First (), one water molecule binds to one of the oxygen atoms of the phosphate group, holding it in the proper orientation for the enzymatic mechanism. Second (), the environment of the active site lowers the pKa of another water molecule enough that it can lose a proton to the aqueous environment.
The now-negatively charged hydroxyl group () removes a proton from the 2' hydroxyl of cytosine 17. This oxygen () then starts to form a bond to the phosphorus atom of the phosphate group.
This is the transition state (). Five oxygen atoms are arranged in a triangular bipyramid around the phosphorus atom. A bond is being formed between the 2' oxygen of cytosine 17 and the phosphorus atom. Simultaneously a bond is being broken between the phosphorus atom and the hydroxyl oxygen of the next nucleotide, adenine 1.1.
Cytosine 17 is left with a 2'-3' cyclic phosphate group (). The 5' nucleotide () recovers a proton from the aqueous environment, completing a hydroxyl group. The reaction products diffuse away from the active site, leaving the ribozyme free to bind its substrate and complete another reaction cycle.

Ribozymes are being studied for potential use as drugs for AIDS and other diseases.


Ribozymes