2IPH

X-ray Structure at 1.75 A Resolution of a Norovirus Protease Linked to an Active Site Directed Peptide Inhibitor

Summary for 2IPH

• Entry DOI: 10.2210/pdb2iph/pdb
• Descriptor: Thiol protease P3C, N-ACETYL-L-ALPHA-GLUTAMYL-L-PHENYLALANYL-L-GLUTAMINYL-N-[(1S)-4-AMINO-1-(2-CARBOXYETHYL)-4-OXOBUTYL]-L-LEUCINAMIDE (3 entities in total)
• Functional Keywords: beta barrel, alpha helix, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Southampton virus (serotype 3)
• Total number of polymer chains: 2
• Total formula weight: 40078.15

Authors

Hussey, R.J. (deposition date: 2006-10-12, release date: 2007-10-23, Last modification date: 2024-11-20)

Primary citation

Hussey, R.J.,Coates, L.,Gill, R.S.,Erskine, P.T.,Coker, S.F.,Mitchell, E.,Cooper, J.B.,Wood, S.,Broadbridge, R.,Clarke, I.N.,Lambden, P.R.,Shoolingin-Jordan, P.M.
A Structural Study of Norovirus 3C Protease Specificity: Binding of a Designed Active Site-Directed Peptide Inhibitor.
Biochemistry, 50:240-249, 2011

PubMed Abstract: Noroviruses are the major cause of human epidemic nonbacterial gastroenteritis. Viral replication requires a 3C cysteine protease that cleaves a 200 kDa viral polyprotein into its constituent functional proteins. Here we describe the X-ray structure of the Southampton norovirus 3C protease (SV3CP) bound to an active site-directed peptide inhibitor (MAPI) which has been refined at 1.7 Å resolution. The inhibitor, acetyl-Glu-Phe-Gln-Leu-Gln-X, which is based on the most rapidly cleaved recognition sequence in the 200 kDa polyprotein substrate, reacts covalently through its propenyl ethyl ester group (X) with the active site nucleophile, Cys 139. The structure permits, for the first time, the identification of substrate recognition and binding groups in a noroviral 3C protease and thus provides important new information for the development of antiviral prophylactics.

PubMed: 21128685
DOI: 10.1021/bi1008497

Experimental method

X-RAY DIFFRACTION (1.75 Å)