The Structure of Human 15-Lipoxygenase-2 with a Substrate Mimic
| Autor: | Sue G. Bartlett, Marcia E. Newcomer, Caitlin E. Mitchell, Matthew J. Kobe, David B. Neau |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Protein Conformation Plasma protein binding Biology Crystallography X-Ray Biochemistry Lipoxygenase Protein structure Oxidoreductase Catalytic Domain Arachidonate 15-Lipoxygenase Humans Binding site Molecular Biology chemistry.chemical_classification Binding Sites food and beverages Substrate (chemistry) Cell Biology Amino acid Enzyme chemistry Protein Structure and Folding biology.protein lipids (amino acids peptides and proteins) Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 289:8562-8569 |
| ISSN: | 0021-9258 |
| Popis: | Atherosclerosis is associated with chronic inflammation occurring over decades. The enzyme 15-lipoxygenase-2 (15-LOX-2) is highly expressed in large atherosclerotic plaques, and its activity has been linked to the progression of macrophages to the lipid-laden foam cells present in atherosclerotic plaques. We report here the crystal structure of human 15-LOX-2 in complex with an inhibitor that appears to bind as a substrate mimic. 15-LOX-2 contains a long loop, composed of hydrophobic amino acids, which projects from the amino-terminal membrane-binding domain. The loop is flanked by two Ca(2+)-binding sites that confer Ca(2+)-dependent membrane binding. A comparison of the human 15-LOX-2 and 5-LOX structures reveals similarities at the active sites, as well striking differences that can be exploited for design of isoform-selective inhibitors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|