4cw4
Crystal structure of the noncanonical ketosynthase FabY from P. aeruginosa
Structural highlights
FunctionFABY_PSEAE Involved in the initiation of the fatty acid biosynthesis. Catalyzes the condensation of acetyl coenzyme A (acetyl-CoA) with malonyl-acyl carrier protein (ACP) to make the fatty acid synthesis (FAS) primer beta-acetoacetyl-ACP. It can also use short-chain acyl-CoA as substrates, including butyryl-CoA, and hexanoyl-CoA, but does not use any of the longer chain acyl-CoA substrates.[1] [2] Publication Abstract from PubMedFungal fatty acid synthase (fFAS) is a key paradigm for the evolution of complex multienzymes. Its 48 functional domains are embedded in a matrix of scaffolding elements, which comprises almost 50% of the total sequence and determines the emergent multienzymes properties of fFAS. Catalytic domains of fFAS are derived from monofunctional bacterial enzymes, but the evolutionary origin of the scaffolding elements remains enigmatic. Here, we identify two bacterial protein families of noncanonical fatty acid biosynthesis starter enzymes and trans-acting polyketide enoyl reductases (ERs) as potential ancestors of scaffolding regions in fFAS. The architectures of both protein families are revealed by representative crystal structures of the starter enzyme FabY and DfnA-ER. In both families, a striking structural conservation of insertions to scaffolding elements in fFAS is observed, despite marginal sequence identity. The combined phylogenetic and structural data provide insights into the evolutionary origins of the complex multienzyme architecture of fFAS. Evolutionary origins of the multienzyme architecture of giant fungal Fatty Acid synthase.,Bukhari HS, Jakob RP, Maier T Structure. 2014 Dec 2;22(12):1775-85. doi: 10.1016/j.str.2014.09.016. Epub 2014, Nov 13. PMID:25456814[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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