The structures of picornaviral proteinases

Seipelt, Joachim; Guarné, Alba; Bergmann, Ernst M.; James, Michael N.G.; Sommergruber, Wolfgang; Fita, Ignacio; Skern, Tim

doi:10.1016/s0168-1702(99)00043-x

Cited by 101 publications

(96 citation statements)

References 52 publications

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“…Primary cleavages of the polyprotein are mediated by the 3C proteinase (3C pro ), a serine-proteinase with a cysteine active site (Seipelt et al, 1999). Enterovirus 3C pro cleaves between Q and G pairs while aphthovirus 3C pro accepts E or Q at the first position .…”

Section: Picornavirus Genome Organizationmentioning

confidence: 99%

Picornavirus IRES elements: RNA structure and host protein interactions

et al. 2015

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Section: Picornavirus Genome Organizationmentioning

confidence: 99%

Picornavirus IRES elements: RNA structure and host protein interactions

et al. 2015

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“…With the exception of the 3A/3B cleavage, each of the 3C pro cleavage sites within the HAV polyprotein possess the consensus sequence (L/V/I)x(T/S)Q2x (31). Such a sequence exists at Gln-428 of MAVS (Fig.…”

Section: Abcmentioning

confidence: 99%

Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor

Yang

Liang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

292

279

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“…The first two domains form a chymotrypsin fold, which is responsible for the catalytic reaction, and the third domain is ␣-helical with unclear biological function. Coronavirus 3C-like proteinase shares the chymotrypsin fold part with the 3C proteinases from other viruses like rhinovirus called picornavirus (7,8). The 3C proteinase of rhinovirus has been used as a target to develop drugs against the common cold (9 -15).…”

mentioning

confidence: 99%

Biosynthesis, Purification, and Substrate Specificity of Severe Acute Respiratory Syndrome Coronavirus 3C-like Proteinase

Fan

Wei

Qian

et al. 2004

Journal of Biological Chemistry

328

422

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The 3C-like proteinase of severe acute respiratory syndrome (SARS) coronavirus has been proposed to be a key target for structural-based drug design against SARS. In order to understand the active form and the substrate specificity of the enzyme, we have cloned, expressed, and purified SARS 3C-like proteinase. Analytic gel filtration shows a mixture of monomer and dimer at a protein concentration of 4 mg/ml and mostly monomer at 0.2 mg/ml, which correspond to the concentration used in the enzyme assays. The linear decrease of the enzymatic-specific activity with the decrease of enzyme concentration revealed that only the dimeric form is active and the dimeric interface could be targeted for structural-based drug design against SARS 3C-like proteinase. By using a high pressure liquid chromatography assay, SARS 3C-like proteinase was shown to cut the 11 peptides covering all of the 11 cleavage sites on the viral polyprotein with different efficiency. The two peptides corresponding to the two self-cleavage sites are the two with highest cleavage efficiency, whereas peptides with non-canonical residues at P2 or P1 positions react slower. The P2 position of the substrates seems to favor large hydrophobic residues. Secondary structure studies for the peptide substrates revealed that substrates with more ␤-sheetlike structure tend to react fast. This study provides a basic understanding of the enzyme catalysis and a full substrate specificity spectrum for SARS 3C-like proteinase, which are helpful for structural-based inhibitor design against SARS and other coronavirus.The outbreak of a severe atypical pneumonia in early 2003 has caused 8422 cases and 916 related deaths. The World Health Organization has designated the illness as severe acute respiratory syndrome (SARS).1 A novel form of coronavirus has been identified as the major cause of SARS (1, 2). The genome of SARS coronavirus has been sequenced within a short period of time after confirmation of the virus (3, 4). Currently, 23 genome sequences of different variations of SARS coronavirus have been released at the NCBI web site (www.ncbi.nlm.nih. gov/). Coronaviruses are members of positive-stranded RNA viruses featuring the largest viral RNA genomes up to date. The SARS coronavirus replicase gene encompasses two overlapping translation products, polyproteins 1a (ϳ450 kDa) and 1ab (ϳ750 kDa), which are conserved both in length and amino acid sequence to other coronavirus replicase proteins. Polyproteins 1a and 1ab are cleaved by the internally encoded 3C-like proteinase to release functional proteins necessary for virus replication. The SARS 3C-like proteinase is fully conserved among all of the released SARS coronavirus genome sequences and is highly homologous with other coronavirus 3C-like proteinase.Two crystal structures of coronavirus 3C-like proteinase from transmissible gastroenteritis virus (TGEV) (5) and human coronavirus (hCoV) 229E have been solved (6). The structure of coronavirus 3C-like proteinase contains three domains. The first two domains form ...

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The structures of picornaviral proteinases

Cited by 101 publications

References 52 publications

Picornavirus IRES elements: RNA structure and host protein interactions

Picornavirus IRES elements: RNA structure and host protein interactions

Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor

Biosynthesis, Purification, and Substrate Specificity of Severe Acute Respiratory Syndrome Coronavirus 3C-like Proteinase

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