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Science 331 (6014): 217-219

Copyright © 2011 by the American Association for the Advancement of Science

The Structure of Human 5-Lipoxygenase

Nathaniel C. Gilbert,1 Sue G. Bartlett,1 Maria T. Waight,1 David B. Neau,2 William E. Boeglin,3 Alan R. Brash,3 Marcia E. Newcomer1,*

Abstract: The synthesis of both proinflammatory leukotrienes and anti-inflammatory lipoxins requires the enzyme 5-lipoxygenase (5-LOX). 5-LOX activity is short-lived, apparently in part because of an intrinsic instability of the enzyme. We identified a 5-LOX–specific destabilizing sequence that is involved in orienting the carboxyl terminus, which binds the catalytic iron. Here, we report the crystal structure at 2.4 angstrom resolution of human 5-LOX stabilized by replacement of this sequence.

1 Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
2 Northeastern Collaborative Access Team, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA.
3 Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

* To whom correspondence should be addressed. E-mail: newcomer{at}lsu.edu


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