Experimental verification of conformational variation of human fatty acid synthase as predicted by normal mode analysis - PubMed (original) (raw)
Experimental verification of conformational variation of human fatty acid synthase as predicted by normal mode analysis
Jacob Brink et al. Structure. 2004 Feb.
Free article
Abstract
Fatty acid synthase (FAS) is a 550 kDa homodimeric enzyme with multiple functional and structural domains. Normal mode analysis of a previously determined 19 A structure of FAS suggested that this enzyme might assume different conformational states with several distinct hinge movements. We have used a simultaneous multiple-model refinement method to search for the presence of the structural conformers from the electron images of FAS. We have demonstrated that the resulting models observed in the electron images are consistent with the predicted conformational changes. This technique demonstrates the potential of the combination of normal mode analysis with multiple model refinement to elucidate the multiple conformations of flexible proteins. Since each of these structures is based on a more homogeneous particle set, this technique has the potential, provided that sufficient references are used, to improve the resolution of the final reconstructions of single particles from electron cryomicroscopy.
Comment in
- Accessing information on the conformational flexibility of molecular machines.
Carazo JM. Carazo JM. Structure. 2004 Feb;12(2):170-1. doi: 10.1016/j.str.2004.01.017. Structure. 2004. PMID: 14962375 No abstract available.
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