PROSITE documentation PDOC00529Ketosynthase family 3 (KS3) active signature and domain profile
In all organisms studied to date, fatty acid synthases (FASs) and polyketide synthases (PKSs) are closely related and have a common evolutionary history. FASs and PKSs share a similar enzymatic domain structure in which acyl transferase (AT), ketosynthase (KS) and an acyl carrier protein (ACP) form the core structure for condensation of acyl units, and are essential for both PKSs and FASs. The other domains, ketoreductases (KR), enoyl reductase (ER) and dehydratase (DH) modify the acyl units after condensation, which is essential for FASs, but selectively present/absent in PKS [1].
Ketoacyl synthases (KSs) (more officially 3-oxoacyl synthases and also known as β-ketoacyl synthases) are the condensing enzymes that catalyze the reaction of acyl-coenzyme A (acyl-CoA) or acyl-acyl carrier protein (acyl-ACP) with malonyl-CoA, malonyl-ACP, or occasionally other substrates. KSs fall into five families separated by their characteristic primary structures, each having members with the same catalytic residues, mechanisms, and tertiary structures. KS3, a very large family, is composed of bacterial and eukaryotic 3-ketoacyl-ACP synthases I and II, often found in multidomain fatty acid and polyketide synthases [2].
The KS3 domain possesses a thiolase fold, comprised of alternating layers of α-helices and β-sheets with α/β/α/β/α-layered architecture (see <PDB:2ALM>). The KS3 domain has a catalytic triad Cys-His-His, in which the cysteine is the nucleophile involved in the trans-thioesterification reactions. The two histidine residues located in the vicinity of the cysteine contribute to the formation of an oxyanion hole that stabilizes the terahedron intermediate and presumably promote the decarboxylation of the extender unit. The catalytic triad is located within a deep pocket that must be accessed by the phospho-pantetheine arm attached to the acyl carrier protein [3,4].
The sequence around the active site cysteine is well conserved and can be used as a signature pattern. We also developed a profile that covers the entire KS family 3 domain.
Last update:March 2023 / Profile revised.
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PROSITE methods (with tools and information) covered by this documentation:
| 1 | Authors | Kohli G.S. John U. Van Dolah F.M. Murray S.A. |
| Title | Evolutionary distinctiveness of fatty acid and polyketide synthesis in eukaryotes. | |
| Source | ISME. J. 10:1877-1890(2016). | |
| PubMed ID | 26784357 | |
| DOI | 10.1038/ismej.2015.263 |
| 2 | Authors | Chen Y. Kelly E.E. Masluk R.P. Nelson C.L. Cantu D.C. Reilly P.J. |
| Title | Structural classification and properties of ketoacyl synthases. | |
| Source | Protein. Sci. 20:1659-1667(2011). | |
| PubMed ID | 21830247 | |
| DOI | 10.1002/pro.712 |
| 3 | Authors | Xu W. Qiao K. Tang Y. |
| Title | Structural analysis of protein-protein interactions in type I polyketide synthases. | |
| Source | Crit. Rev. Biochem. Mol. Biol. 48:98-122(2013). | |
| PubMed ID | 23249187 | |
| DOI | 10.3109/10409238.2012.745476 |
| 4 | Authors | Abdel-Hameed M.E. Bertrand R.L. Donald L.J. Sorensen J.L. |
| Title | Lichen ketosynthase domains are not responsible for inoperative polyketide synthases in Ascomycota hosts. | |
| Source | Biochem. Biophys. Res. Commun. 503:1228-1234(2018). | |
| PubMed ID | 30007436 | |
| DOI | 10.1016/j.bbrc.2018.07.029 |
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