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

Abstract

Evidence is presented, based on sequence comparison and secondary structure prediction, of structural and evolutionary relationship between chymotrypsin-like serine proteases, cysteine proteases of positive strand RNA viruses (3C proteases of picornaviruses and related enzymes of come-, nepo-and potyviruses) and putative serine protease of a sobemovirus. These observations lead to re-identification of principal catalytic residues of viral proteases. Instead of the pair of Cys and His, both located in the C-terminal part of 3C proteases, a triad of conserved His, Asp(Glu) and Cys(Ser) has been identified, the first two residues resident in the N-terminal, and Cys in the C-terminal fl-barrel domain. These residues are suggested to form a charge-transfer system similar to that formed by the catalytic triad of chymotrypsin-like proteases. Based on the structural analogy with chymotrypsin-like proteases, the His residue previously implicated in catalysis, together with two partially conserved Gly residues, is predicted to constitute part of the substrate-binding pocket of 3C proteases. A partially conserved ThrLys/Arg dipeptide located in the loop preceding the catalytic Cys is suggested to confer the primary cleavage specificity of 3C toward Glx/Gly(Ser) sites. These observations provide the first example of relatedness between proteases belonging, by definition, to different classes.

Secoviridae: a proposed family of plant viruses within the order Picornavirales that combines the families Sequiviridae and Comoviridae, the unassigned genera Cheravirus and Sadwavirus, and the proposed genus Torradovirus

“…Each genome segment encodes a large polyprotein. This polyprotein is cleaved by cysteine proteinases (such as the picornavirus 3C proteinase) that are structurally related to chymotrypsin [1,9,13]. The genome organization is conserved among picornavirales.…”

Characterization of the S1 binding site of the glutamic acid‐specific protease from Streptomyces griseus

“…SGPE and the human rhinovirus 3C proteinase (3CPr0) both have a trypsin-like three-dimensional fold, although the latter is a thiol protease (Nienaber et al, 1993;Matthews et al, 1994). The specificity of 3CPr0 is assumed to be due to interactions between the carboxyamide group of the PI glutamine and the side-chains of the highly conserved Thr 141 and His 160 (one acting as a hydrogen bond donor and the other as an acceptor) (Bazan & Fletterick, 1988;Gorbalenya et al, 1989;Matthews et al, 1994 (Nienaber et al, 1993;Matthews et al, 1994). However, in SGPE, both residues act as hydrogen bond donors and it is conceivable that this can explain the different specificities of the two classes of enzymes.…”

Inhibitory effect of oryzacystatins and a truncation mutant on the replication of poliovirus in infected Vero cells

“…There are at least two ways to explain this result. First, E-64 and its analogues might be unable to inhibit viral proteinases even though they effectively inhibit typical cysteine proteinases such as papain and cathepsin H. Even though it contains cysteine and histidine residues in its active site, cysteine proteinase of poliovirus might be a prototype of either a serine or cysteine proteinase, in which ease it would resemble ehymotrypsin rather than papain [16,17]. Compared to E-64, cystatins might have a wider inhibitory spectrum allowing them to inhibit viral cysteine proteinases.…”