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

FEBS Letters

Gorbalenya, Alexander E.¹  Koonin, Eugene V.¹  Blinov, Vladimir M.¹  Donchenko, Alexei P.¹ 

[1] Institute of Poliomyelitis and Viral Encephalitides of the USSR Academy of Medical Sciences, 142782 Moscow Region, USSR

关键词: Serine protease;    Cysteine protease;    Amino acid sequence comparison;    Protein fold prediction;    Positive strand RNA virus;    PV1;    poliovirus type 1;    HRV1a;    human rhinovirus type 1a;    HRV2;    human rhinovirus type 2;    HRV14;    human rhinovirus type 14;    CVB3;    coxsackie virus type B3;    ECHO;    echovirus type 9;    BEV;    bovine enterovirus;    TMEV;    Theiler murine encephalomyelitis virus;    EMCV;    encephalomyocarditis virus;    FMDV;    foot-and-mouth disease virus type A10;    HAV;    hepatitis A virus (picornaviruses);    CPMV;    cowpea mosaic virus (comovirus);    TBRV;    tomato black ring virus (nepovirus);    TVMV;    tobacco vein mottling virus;    TEV;    tobacco etch virus (potyviruses);    SBMV;    southern bean mosaic virus (sobemovirus);    SGPA;    Streptomyces griseus protease A;    SGPB;    Streptomyces griseus protease B;    CHT;    chymotryptin;    TRP;    trypsin;    ELA;    elastase (chymotrypsin-like proteases);   

DOI  :  10.1016/0014-5793(89)80109-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 como-, 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 β-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.

【 授权许可】

Unknown