The structure of human 5-lipoxygenase.

Publication Type:

Journal Article

Authors:

Gilbert, Nathaniel C; Bartlett, Sue G; Waight, Maria T; Neau, David B; Boeglin, William E; Brash, Alan R; Newcomer, Marcia E

Source:

Science, Volume 331, Issue 6014, p.217-9 (2011)

Keywords:

Amino Acid Sequence, Arachidonate 5-Lipoxygenase, Catalytic Domain, Crystallography, X-Ray, Enzyme Stability, Humans, Iron, Models, Molecular, Molecular Sequence Data, Mutant Proteins, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary

Abstract:

<p>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.</p>