Controlling Inflammation

Science Signaling  18 Jan 2011:
Vol. 4, Issue 156, pp. ec22
DOI: 10.1126/scisignal.4156ec22

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.

N. C. Gilbert, S. G. Bartlett, M. T. Waight, D. B. Neau, W. E. Boeglin, A. R. Brash, M. E. Newcomer, The structure of human 5-lipoxygenase. Science 331, 217–219 (2011). [Abstract] [Full Text]