Poliovirus‐encoded proteinase 3C: a possible evolutionary link between cellular serine and cysteine proteinase families

Abstract

Here we demonstrate significant similarities between the amino acid sequences of trypsin (a serine protease) and the N-terminal piece of a specific fragment of the poliovirus polyprotein encompassing the sequence of the viral proteinase 3C, and also between cathepsin H (a cysteine protease) and the C-terminal piece of the same fragment. A coherent alignment of the sequences of the 3 proteases was obtained, in which the principal catalytically active residues occupy identical positions. A hypothesis is proposed that the viral enzyme may provide an evolutionary link between serine and cysteine protease families.

Cysteine proteases of positive strand RNA viruses and chymotrypsin‐like serine proteases

“…The similarity of sequence stretches surrounding the (putative) catalytic Cys residues of 3C Pr° to those around the catalytic Ser of chymotrypsin-like proteases has been noticed and discussed previously [11]. These observations prompted a further, more detailed comparison between the two enzyme families.…”

“…Due to the different location of the (putative) catalytic Cys residues and to the lack of overall sequence similarity, it was suggested that 3C-like proteases were not evolutionarily related to other cysteine proteases [5], their formal analogy being explained by convergence. The considerable similarity between the regions of 3C proteases around the putative catalytic Cys to those surrounding the catalytic Set of chymotrypsin-like proteases noticed by us [10,11] was also attributed to convergence [8]. Hence, the general consensus that 3C-like proteases constitute an entirely independent enzyme family.…”

“…It is not clear at present what was the nature of the hypothetical ancestor protease. However, we have argued in previous papers that 3C Pr° have some features which could be expected in a primordial protease [11,35]. Interestingly, it has been very recently proposed, starting from quite different observations, that Cys might be the predecessor of Ser in the catalytic sites of enzymes of several classes [36].…”

Mapping of Functional Domains in Eukaryotic Protein Synthesis Initiation Factor 4G (eIF4G) with Picornaviral Proteases

“…The peaks in fractions 40-50 contained cp N2 and cp N3 and were well resolved from the peak in fractions 51-56, which contained cp N1 . Although cp N2 and cp N3 eluted in the same general region, it was possible to resolve the majority of the cp N2 (fractions 44-47) from the cp N3 (fractions [40][41][42][43]. cp N2 was subjected to N-terminal sequence analysis by automated Edman degradation (Table I).…”

“…The 2A proteases of rhino-and enteroviruses are small thiol proteases with structural similarities to chymotrypsin and α-lytic protease (39)(40)(41). The primary cleavage site in rabbit eIF4G is Arg 486 -Gly 487 (15), although a secondary site of unknown location has been suggested for the 2A protease of HRV2 (12).…”