1N8Q

LIPOXYGENASE IN COMPLEX WITH PROTOCATECHUIC ACID

Summary for 1N8Q

• Entry DOI: 10.2210/pdb1n8q/pdb
• Related: 1BYT 1HU9 1IK3 1LNH 1LOX 1YGE
• Descriptor: lipoxygenase-3, FE (II) ION, 3,4-DIHYDROXYBENZOIC ACID, ... (4 entities in total)
• Functional Keywords: oxidoreductase, lipoxygenase, iron, protocatechuic acid, 3, 4-dihydroxybenzoic acid, lox complex, quercetin
• Biological source: Glycine max (soybean)
• Cellular location: Cytoplasm: P09186
• Total number of polymer chains: 1
• Total formula weight: 97128.96

Authors

Borbulevych, O.Y.,Jankun, J.,Selman, S.H.,Skrzypczak-Jankun, E. (deposition date: 2002-11-21, release date: 2003-06-03, Last modification date: 2023-08-16)

Primary citation

Borbulevych, O.Y.,Jankun, J.,Selman, S.H.,Skrzypczak-Jankun, E.
Lipoxygenase interactions with natural flavonoid, quercetin, reveal a complex with protocatechuic acid in its X-ray structure at 2.1 A resolution.
PROTEINS: STRUCT.,FUNCT.,GENET., 54:13-19, 2004

PubMed Abstract: 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.

PubMed: 14705020
DOI: 10.1002/prot.10579

Experimental method

X-RAY DIFFRACTION (2.1 Å)