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Curry Lab
Biophysics Section |
HSA in Motion |
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HSA is a remarkably flexible molecule. Our work is helping to reveal the structural changes due to fatty acid binding and the impact that this has on other ligand such as drugs. The animations on this page should help to illustrate what happens to HSA when fatty acids bind. However, please note that these animations are 'morphs' (see reference below) made using the known structures of defatted HSA and the HSA-myristate complex. They give an indication of a possible path for the structural transition upon fatty acid binding. Although we can be sure of the starting and ending structures we have no direct experimental information on how the transition is achieved. Click on the thumbnails below to see each animation. Animations are in Quicktime format. If they don’t play, get Quicktime free from Apple for Mac or PC. |
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Top view of the global conformational changes in HSA that occur on fatty acid binding. The changes can mostly easily be thought of as rotations of domains I and III relative to domain II since there are no gross distortions of the protein backbone within each domain when fatty acids bind. The same conformational change is observed for fatty acids ranging in length from C10 to C20. |
Global view of fatty acid induced conformational changes in HSA |
Top view |
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Close-up of changes at the interface between domains I and II |
Close-up of changes at the interface between domains II and III |
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Local changes in subdomain IB upon fatty acid binding |
Changes at the warfarin binding site on fatty acid binding |
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Animations were prepared using the morphing utilities in LSQMAN [See Kleywegt, G.J. (1996). Use of non-crystallographic symmetry in protein structure refinement. Acta Cryst., D52, 842-857.] |
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Feb 2008 |
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