Structural Organization of the Regulatory Domain of Human 5- Lipoxygenase

Title: Structural Organization of the Regulatory Domain of Human 5- Lipoxygenase

Volume: 6 Issue: 2

Author(s): John B. Allard and Thomas G. Brock

Affiliation:

Keywords: 5-lipoxygenase, structure, c2 domain, toxin, lipase, protein kinase c, sandwich, plat domain

Abstract: 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 β-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, α-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.

Cite this article as:

Allard B. John and Brock G. Thomas, Structural Organization of the Regulatory Domain of Human 5- Lipoxygenase, Current Protein & Peptide Science 2005; 6 (2) . https://dx.doi.org/10.2174/1389203053545417