Sci. Signal., 18 January 2011
Biochemistry Controlling Inflammation
Science, AAAS, Washington, DC 20005, USA
Lipids that mediate the inflammatory response are synthesized from arachidonic acid by the enzyme 5-lipoxygenase (5-LOX). An intrinsic instability of 5-LOX has been proposed to regulate its activity. Structures of related enzymes have shown that the C terminus penetrates the enzyme so that the main chain carboxylate of the C-terminal residue binds the catalytic iron. Gilbert et al. identified a sequence that probably destabilizes the orientation of the C terminus in 5-LOX and, by substituting this sequence, were able to purify a stable enzyme and determine its crystal structure. The structure is consistent with the proposed mechanism of enzyme inactivation and provides a basis for the design of 5-LOX–specific inhibitors.
Citation: V. Vinson, Controlling Inflammation. Sci. Signal. 4, ec22 (2011).
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