5XG4

Crystal structure of uPA in complex with quercetin

Summary for 5XG4

• Entry DOI: 10.2210/pdb5xg4/pdb
• Descriptor: Urokinase-type plasminogen activator, 3,5,7,3',4'-PENTAHYDROXYFLAVONE, 1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE, ... (4 entities in total)
• Functional Keywords: serine proteases, upa, pepetide inhibitors, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted: P00749
• Total number of polymer chains: 1
• Total formula weight: 28284.17

Authors

Jiang, L.,Huang, M. (deposition date: 2017-04-11, release date: 2017-07-26, Last modification date: 2024-11-13)

Primary citation

Xue, G.,Gong, L.,Yuan, C.,Xu, M.,Wang, X.,Jiang, L.,Huang, M.
A structural mechanism of flavonoids in inhibiting serine proteases
Food Funct, 8:2437-2443, 2017

PubMed Abstract: Quercetin is a member of the flavonoids and was previously demonstrated to inhibit trypsin-like serine proteases at micromolar potencies. Different molecular models were proposed to explain such inhibition. However, controversies remain on the molecular details of inhibition. Here, we report the X-ray crystal structure of quercetin in a complex with the urokinase-type plasminogen activator (uPA), an archetypical serine protease. The structure showed that quercetin binds to the specific substrate binding pocket (S1 pocket) of uPA mainly through its two neighboring phenolic hydroxyl groups. Our study thus provides unambiguous evidence to support quercetin binding to serine proteases and defines the molecular basis of the interaction. Our results further establish that natural products with two adjacent phenolic hydroxyl groups (or catechol) are likely to inhibit other trypsin-like serine proteases, a new mechanism formerly under-recognized.

PubMed: 28644504
DOI: 10.1039/c6fo01825d

Experimental method

X-RAY DIFFRACTION (3 Å)