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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Arachidonate 5-Lipoxygenase / chemistry*
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Arachidonate 5-Lipoxygenase / genetics
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Arachidonate 5-Lipoxygenase / metabolism
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Catalytic Domain
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Crystallography, X-Ray
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Enzyme Stability
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Humans
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Iron / chemistry
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Iron / metabolism
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Models, Molecular
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Molecular Sequence Data
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Mutant Proteins / chemistry
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Protein Folding
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Protein Structure, Secondary
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Protein Structure, Tertiary
Substances
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Mutant Proteins
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Iron
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Arachidonate 5-Lipoxygenase