Structural organization of the regulatory domain of human 5-lipoxygenase.
The enzyme 5-lipoxygenase (5-LO) initiates the synthesis of leukotrienes. For this reason, 5-LO activity is important for immune defense, whereas improper regulation contributes to pathogenesis, including chronic inflammation, asthma and atherosclerosis. Like all lipoxygenases, the 5-LO protein consists of two domains, a regulatory domain and a catalytic domain. Naturally, the regulatory domain determines catalytic activity and controls leukotriene synthesis. This domain shares features with classical C2 domains in that it has a beta-sandwich structure and binds calcium, nucleotides and phospholipids. However, important structural features place this domain in a distinct family, the PLATs (for Polycystin-1, Lipoxygenase, alpha-Toxin). In this review, we summarize our current understanding of the three dimensional organization of this important component of the 5-LO molecule. In addition, we point to findings from structural analyses of related proteins to suggest further details relating 5-LO structure to function.
Allard
John B
JB
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0642, USA.
Brock
Thomas G
TG
D000595:Amino Acid Sequence; D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
D015289:Leukotrienes; D001094:Arachidonate 5-Lipoxygenase; D002118:Calcium