5GWZ

The structure of Porcine epidemic diarrhea virus main protease in complex with an inhibitor

Summary for 5GWZ

• Entry DOI: 10.2210/pdb5gwz/pdb
• Related PRD ID: PRD_002214
• Descriptor: PEDV main protease, N-[(5-METHYLISOXAZOL-3-YL)CARBONYL]ALANYL-L-VALYL-N~1~-((1R,2Z)-4-(BENZYLOXY)-4-OXO-1-{[(3R)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-L-LEUCINAMIDE (3 entities in total)
• Functional Keywords: pedv, main protease, inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Porcine epidemic diarrhea virus CV777 (PEDV); More
• Total number of polymer chains: 4
• Total formula weight: 67694.58

Authors

Wang, F.,Chen, C.,Yang, K.,Liu, X.,Liu, H.,Xu, Y.,Chen, X.,Liu, X.,Cai, Y.,Yang, H. (deposition date: 2016-09-14, release date: 2017-03-29, Last modification date: 2024-10-23)

Primary citation

Wang, F.,Chen, C.,Yang, K.,Xu, Y.,Liu, X.,Gao, F.,Liu, H.,Chen, X.,Zhao, Q.,Liu, X.,Cai, Y.,Yang, H.
Michael Acceptor-Based Peptidomimetic Inhibitor of Main Protease from Porcine Epidemic Diarrhea Virus
J. Med. Chem., 60:3212-3216, 2017

PubMed Abstract: Porcine epidemic diarrhea virus (PEDV) causes high mortality in pigs. PEDV main protease (M) plays an essential role in viral replication. We solved the structure of PEDV M complexed with peptidomimetic inhibitor N3 carrying a Michael acceptor warhead, revealing atomic level interactions. We further designed a series of 17 inhibitors with altered side groups. Inhibitors M2 and M17 demonstrated enhanced specificity against PEDV M. These compounds have potential as future therapeutics to combat PEDV infection.

PubMed: 28287727
DOI: 10.1021/acs.jmedchem.7b00103

Experimental method

X-RAY DIFFRACTION (2.444 Å)