3-ketoacyl-coA thiolase 2
Arabidopsis thaliana (mouse-ear cress)
In daily life, we eat food such as proteins, polysaccharides (carbohydrates) and fats, as main source for getting energy and making our body. These should be broken down into small molecules before our cells can use them; proteins into amino acids, polysaccharides into sugars (glucose) and fats into fatty acid and glycerol - through the action of enzymes. Proteins are mainly used as building blocks such as enzymes and constituent of cells. In contrast, polysaccharides and fats provide the major energy source for most non-photosynthetic organisms, including humans. Especially, fats can create two times more energy than glucose. Fatty acids from fats and glucose from polysaccharides are converted to acetyl CoA in cells via different pathways. Then acetyl CoA is used to get much energy by following reactions.
For degrading fatty acids, four enzymes contribute. Each molecule of fatty acid (as the activated molecule fatty acyl CoA) is broken down completely by a cycle of reactions that trim two carbons at a time from its carboxyl end, generating one molecule of acetyl CoA for each turn of the cycle, which is called beta-oxydation reaction.
The structure shown here is one of the four enzymes, which acts at the last step of the reactions, 3-ketoacyl-CoA thiolase of peroxisomal Arabidopsis thaliana. The overall structure is typical for thiolases, composed of a combination of two similar I/III domains capped a loop domain II. Domain I and II consist of a buried beta-sheet with two helices on one side at the surface of the subunit and single amphipathic helix on the other. Domain II, the lid domain, is an extended structure covering a large surface area of the enzyme. The active site for catalyzing reaction is located at the center of three domains. In this structure, a helix of the lid domain lies within the active site, blocking access of ligands. By comparing with the report of Saccharomyces cerevisiae crystallized in reduced condition, this structure represents an oxidized and inactive form. Taken together, these results suggest that fatty acid beta-oxidation would be controlled by redox chemistry.
Protein Data Bank (PDB)
Sundaramoorthy, R. Micossi, E. Alphey, M.S. Germain, V. Bryce, J.H. Smith, S.M. Leonard, G.A. Hunter, W.N.; "The Crystal Structure of a Plant 3-Ketoacyl-Coa Thiolase Reveals the Potential for Redox Control of Peroxisomal Fatty Acid Beta-Oxidation."; J.Mol.Biol.; (2006) 359:347-.
author: Sachiyo Nomura