4QBB

Structure of the foot-and-mouth disease virus leader proteinase in complex with inhibitor (N~2~-[(3S)-4-({(2R)-1-[(4-CARBAMIMIDAMIDOBUTYL)AMINO]-4-METHYL-1-OXOPENTAN-2-YL}AMINO)-3-HYDROXY-4-OXOBUTANOYL]-L-ARGINYL-L-PROLINAMIDE)

Summary for 4QBB

• Entry DOI: 10.2210/pdb4qbb/pdb
• Related: 1QMY
• Descriptor: Leader protease, POTASSIUM ION, N~2~-[(3S)-4-({(2R)-1-[(4-carbamimidamidobutyl)amino]-4-methyl-1-oxopentan-2-yl}amino)-3-hydroxy-4-oxobutanoyl]-L-arginyl-L-prolinamide, ... (5 entities in total)
• Functional Keywords: papain-like cysteine proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Foot-and-mouth disease virus (FMDV)
• Cellular location: Protein VP2: Virion. Protein VP3: Virion. Protein VP1: Virion. Protein 2B: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 2C: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 3A: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 3B-1: Virion . Protein 3B-2: Virion . Protein 3B-3: Virion . Picornain 3C: Host cytoplasm . RNA-directed RNA polymerase 3D-POL: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side : P03305
• Total number of polymer chains: 3
• Total formula weight: 59135.22

Authors

Grishkovskaya, I.,Steinberger, J.,Cencic, R.,Juliano, M.A.,Juliano, L.,Skern, T. (deposition date: 2014-05-07, release date: 2014-11-05, Last modification date: 2024-11-06)

Primary citation

Steinberger, J.,Grishkovskaya, I.,Cencic, R.,Juliano, L.,Juliano, M.A.,Skern, T.
Foot-and-mouth disease virus leader proteinase: Structural insights into the mechanism of intermolecular cleavage.
Virology, 468-470C:397-408, 2014

PubMed Abstract: Translation of foot-and-mouth disease virus RNA initiates at one of two start codons leading to the synthesis of two forms of leader proteinase L(pro) (Lab(pro) and Lb(pro)). These forms free themselves from the viral polyprotein by intra- and intermolecular self-processing and subsequently cleave the cellular eukaryotic initiation factor (eIF) 4 G. During infection, Lb(pro) removes six residues from its own C-terminus, generating sLb(pro). We present the structure of sLb(pro) bound to the inhibitor E64-R-P-NH2, illustrating how sLb(pro) can cleave between Lys/Gly and Gly/Arg pairs. In intermolecular cleavage on polyprotein substrates, Lb(pro) was unaffected by P1 or P1' substitutions and processed a substrate containing nine eIF4GI cleavage site residues whereas sLb(pro) failed to cleave the eIF4GI containing substrate and cleaved appreciably more slowly on mutated substrates. Introduction of 70 eIF4GI residues bearing the Lb(pro) binding site restored cleavage. These data imply that Lb(pro) and sLb(pro) may have different functions in infected cells.

PubMed: 25240326
DOI: 10.1016/j.virol.2014.08.023

Experimental method

X-RAY DIFFRACTION (1.6 Å)