1n8q
From Proteopedia
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LIPOXYGENASE IN COMPLEX WITH PROTOCATECHUIC ACID
Overview
PUFA metabolites have a profound effect on inflammatory diseases and, cancer progression. Blocking their production by inhibiting PUFA, metabolizing enzymes (dioxygenases: cyclooxygenases and LOXs) might be a, successful way to control and relieve such problems, if we learn to better, understand their actions at a molecular level. Compounds with strong, antioxidative and free radical scavenging properties, such as polyphenols, could be effective in blocking PUFA activities, and natural flavonoids, possess such qualities. Quercetin belongs to the group of natural, catecholic compounds and is known as a potent, competitive inhibitor of, LOX. Structural analysis reveals that quercetin entrapped within LOX, undergoes degradation, and the resulting compound has been identified by, X-ray analysis as protocatechuic acid (3,4-dihydroxybenzoic acid), positioned near the iron site. Its C3-OH group points toward His523, C4-OH, forms a hydrogen bond with O=C from the enzyme's C-terminus, and the, carboxylic group is incorporated into the hydrogen bonding network of the, active-site neighborhood via Gln514. This unexpected result, together with, our previous observations concerning other polyphenols, yields new, evidence about the metabolism of natural flavonoids. These compounds might, be vulnerable to the co-oxidase activity of LOX, leading to, enzyme-stimulated oxidative degradation, which results in an inhibitor of, a lower molecular weight.
About this Structure
1N8Q is a Single protein structure of sequence from Glycine max with FE2 and DHB as ligands. Active as Lipoxygenase, with EC number 1.13.11.12 Full crystallographic information is available from OCA.
Reference
Lipoxygenase interactions with natural flavonoid, quercetin, reveal a complex with protocatechuic acid in its X-ray structure at 2.1 A resolution., Borbulevych OY, Jankun J, Selman SH, Skrzypczak-Jankun E, Proteins. 2004 Jan 1;54(1):13-9. PMID:14705020
Page seeded by OCA on Tue Nov 20 22:03:15 2007
