5WEJ

1.95 A resolution structure of Norovirus 3CL protease in complex with a dipeptidyl oxazolidinone-based inhibitor

Summary for 5WEJ

• Entry DOI: 10.2210/pdb5wej/pdb
• Descriptor: Genome polyprotein, (2S)-2-{(5S)-5-[(3-chlorophenyl)methyl]-2-oxo-1,3-oxazolidin-3-yl}-4-methyl-N-{(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}pentanamide (3 entities in total)
• Functional Keywords: protease, norovirus, norwalk virus, antiviral inhibitors, oxazolidinone-based dipeptidyl inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Norwalk virus (Hu/NV/NV/1968/US)
• Total number of polymer chains: 2
• Total formula weight: 41180.17

Authors

Lovell, S.,Battaile, K.P.,Mehzabeen, N.,Damalanka, V.C.,Kim, Y.,Kankanamalage, A.C.G.,Rathnayake, A.D.,Nguyen, H.N.,Chang, K.O.,Groutas, W.C. (deposition date: 2017-07-10, release date: 2017-12-13, Last modification date: 2024-11-20)

Primary citation

Damalanka, V.C.,Kim, Y.,Galasiti Kankanamalage, A.C.,Rathnayake, A.D.,Mehzabeen, N.,Battaile, K.P.,Lovell, S.,Nguyen, H.N.,Lushington, G.H.,Chang, K.O.,Groutas, W.C.
Structure-guided design, synthesis and evaluation of oxazolidinone-based inhibitors of norovirus 3CL protease.
Eur J Med Chem, 143:881-890, 2017

PubMed Abstract: Acute nonbacterial gastroenteritis caused by noroviruses constitutes a global public health concern and a significant economic burden. There are currently no small molecule therapeutics or vaccines for the treatment of norovirus infections. A structure-guided approach was utilized in the design of a series of inhibitors of norovirus 3CL protease that embody an oxazolidinone ring as a novel design element for attaining optimal binding interactions. Low micromolar cell-permeable inhibitors that display anti-norovirus activity have been identified. The mechanism of action, mode of binding, and structural rearrangements associated with the interaction of the inhibitors and the enzyme were elucidated using X-ray crystallography.

PubMed: 29227928
DOI: 10.1016/j.ejmech.2017.12.014

Experimental method

X-RAY DIFFRACTION (1.95 Å)