Perspectives on the evolution, assembly and conformational dynamics of fatty acid synthase type I (FAS I) systems

M Grininger - Current Opinion in Structural Biology, 2014 - Elsevier
Current Opinion in Structural Biology, 2014Elsevier
Highlights•Type I fatty acid synthesis is performed in two essentially different structural
frames.•The assembly of FAS I systems is not understood except of some essential steps for
fungal FAS I.•FAS I systems are conformationally dynamic, which is of inherent importance
for protein function.•Substrate shuttling is based on a well-tuned interplay between the
mobile carrier protein and the catalytic framework.•Interference in the structural integrity
should be evaluated as a new concept for FAS I inhibition.Recently, atomic models of the …
Highlights
  • Type I fatty acid synthesis is performed in two essentially different structural frames.
  • The assembly of FAS I systems is not understood except of some essential steps for fungal FAS I.
  • FAS I systems are conformationally dynamic, which is of inherent importance for protein function.
  • Substrate shuttling is based on a well-tuned interplay between the mobile carrier protein and the catalytic framework.
  • Interference in the structural integrity should be evaluated as a new concept for FAS I inhibition.
Recently, atomic models of the mammalian, fungal and the bacterial fatty acid synthases type I (FAS I) were reported. Now, a wealth of functional data, collected during the last decades, can be embedded into structural frames. But there is more, which remains to be done! Our current considerations are implicitly very much based on a static view onto these proteins. The next step is to include the dynamic processes, which are essential for the function of FAS I. In this perspective, aspects of the current knowledge are reviewed and presented as the basis for the scientific challenges in a new epoch of FAS research.
Elsevier
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