Cysteine/Serine proteases


- Ser-endopeptidase EC.3.4.21.-
- Cys-endopeptidase EC.3.4.22.-
Origins of peptidases
Neil D Rawlings, Alex Bateman
Biochimie. 2019 Nov;166:4-18.
Cryo-EM structures of the SARS-CoV-2 endoribonuclease Nsp15 reveal insight into nuclease specificity and dynamics
Monica C Pillon, Meredith N Frazier, Lucas B Dillard, Jason G Williams, Seda Kocaman, Juno M Krahn, Lalith Perera, Cassandra K Hayne, Jacob Gordon, Zachary D Stewart, Mack Sobhany, Leesa J Deterding, Allen L Hsu, Venkata P Dandey, Mario J Borgnia, Robin E Stanley
Nat Commun. 2021 Jan 27;12(1):636
Mechanism
The active site of a cysteine/serine protease consists of three key amino acids: cysteine/serine, histidine, and aspartate. Together, these residues form a catalytic triad that facilitates the cleavage of peptide bonds in proteins. The cysteine/serine residue acts as a nucleophile, attacking the carbonyl carbon of the peptide bond, while the histidine and aspartate residues assist the process by stabilizing the reaction intermediates.
Genome | Order | Family | Function | Type | MEROPS family | Distribution (low incidence) | Clan (fold) | Interpro | UniProt exemplar |
---|---|---|---|---|---|---|---|---|---|
dsDNA | Chitovirales | ![]() ![]() |
Virion maturation | Cysteine | Peptidase C57 | Virus | CE (Papain fold) | IPR004970 | Core protease OPG083 |
dsDNA | Rowavirales | ![]() ![]() |
Virion maturation | Cysteine | Peptidase C5 | Virus, (animals, bacteria) | CE (Papain fold) | IPR000855 | Adenain |
dsDNA | Lefavirales | ![]() |
Host cell liquefaction | Cysteine | Peptidase C1A | Animals, plant, protozoa, bacteria, archaea, virus | CA (Papain fold) | IPR013128 | Cathepsin |
dsDNA | Pimascovirales | ![]() |
Unknown | Cysteine | Peptidase C14 | Animals, plant, protozoa, bacteria, archaea, virus | CD (Caspase fold) | IPR011600 | Caspase-like protein |
dsDNA | Asfuvirales | ![]() |
Virion maturation | Cysteine | Peptidase C48 | Animals, plant, protozoa, bacteria, archaea, virus | CE (Papain fold) | IPR003653 | Cysteine protease S273R |
dsDNA | Pimascovirales | ![]() |
Unknown | Cysteine | Peptidase C1A | Animals, plant, protozoa, bacteria, archaea, virus | CA (Papain fold) | IPR013128 | Cysteine proteinase 024R |
dsDNA | Imitervirales | ![]() |
Unknown | Cysteine | Peptidase C48 | Animals, plant, protozoa, bacteria, archaea, virus | CE (Papain fold) | IPR003653 | Thiol protease R355 |
dsDNA | unassigned | ![]() |
Unknown | Cysteine | Peptidase C1A | Animals, plant, protozoa, bacteria, archaea, virus | CA (Papain fold) | IPR013128 | Peptidase |
ssRNA+ | Hepevirales | ![]() ![]() |
Polyprotein major protease | Cysteine | ND | Virus | unasigned, CA?![]() |
IPR008748 | POLN |
ssRNA+ | Hepevirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C36 | Virus | unassigned | IPR008746 | ORF1 |
ssRNA+ | Hepevirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C27 | Virus | unassigned | IPR008738 | NSpolyprotein |
ssRNA+ | Martellivirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C42 | Virus | unassigned | IPR008749 | Replicase polyprotein |
ssRNA+ | Martellivirales | ![]() |
Polyprotein major protease | Cysteine | papain-like | Virus | CA (Papain fold) | IPR038765 | Protease |
ssRNA+ | Martellivirales | ![]() ![]() |
Polyprotein major protease | Cysteine | Peptidase C9 | Virus | CN | IPR002620 | POLN |
ssRNA+ | Nidovirales | ![]() ![]() |
Polyprotein major protease | Cysteine | Peptidase C30 | Virus | PA (chymotrypsin fold) | IPR008740 | polyprotein 1ab, 3CL pro |
ssRNA+ | Nidovirales | ![]() ![]() |
Polyprotein Nter protease | Cysteine | Peptidase C16 | Virus | CA (Papain fold) | IPR013016 | polyprotein 1ab, PLpro |
ssRNA+ | Nidovirales | ![]() |
Host antiviral response modulation | Cysteine | Peptidase C31 | Virus | CA (Papain fold) | IPR008741 | polyprotein 1ab, nsp1 alpha |
ssRNA+ | Nidovirales | ![]() |
Host inhibition of translation | Cysteine | Peptidase C32 | Virus | CA (Papain fold) | IPR025773 | polyprotein 1ab, nsp1 beta |
ssRNA+ | Nidovirales | ![]() |
Self-cleavage N-ter polyprotein, host modulation by de-ubiquitination | Cysteine | Peptidase C33 | Virus | CA (Papain fold) | IPR008743 | polyprotein 1ab, nsp2 |
ssRNA+ | Nidovirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C107 | Virus | PA (chymotrypsin fold) | IPR033777 | not annotated |
ssRNA+ | Nidovirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C62 | Virus | PA (chymotrypsin fold) | IPR024348 | polyprotein 1ab |
ssRNA+ | Nidovirales | ![]() ![]() |
Self-cleavage N-ter polyprotein | Cysteine | papain-like | Virus | CA (Papain fold) | IPR038765 | polyprotein 1ab |
ssRNA+ | Picornavirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C37 | Virus | PA (chymotrypsin fold) | IPR001665 | Polyprotein |
ssRNA+ | Picornavirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C24 | Virus | PA (chymotrypsin fold) | IPR000317 | Polyprotein |
ssRNA+ | Picornavirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C3 | Virus, (animals) | PA (chymotrypsin fold) | IPR044067 | Polyprotein |
ssRNA+ | Picornavirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C3 | Virus, (animals) | PA (chymotrypsin fold) | IPR044067 | Polyprotein |
ssRNA+ | Picornavirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C99 | Virus | PA (chymotrypsin fold) | IPR009003 | Polyprotein |
ssRNA+ | Picornavirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C3 | Virus, (animals) | PA (chymotrypsin fold) | IPR044067 | Polyprotein |
ssRNA+ | Picornavirales | ![]() |
Early polyprotein protease | Cysteine | Peptidase C3 | Virus, (animals) | PA (chymotrypsin fold) | IPR044067 | Polyprotein, 2A |
ssRNA+ | Picornavirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C3 | Virus, (animals) | PA (chymotrypsin fold) | IPR044067 | Polyprotein, 3Cpro |
ssRNA+ | Picornavirales | ![]() |
Self cleavage N-ter polyprotein, host antiviral response modulation | Cysteine | Peptidase C28 | Virus | CA (Papain fold) | IPR008739 | Polyprotein, L |
ssRNA+ | Picornavirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase | Virus | PA (chymotrypsin fold) | IPR044067 | Polyprotein |
ssRNA+ | Picornavirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C3 | Virus, (animals) | PA (chymotrypsin fold) | IPR044067 | Polyprotein |
ssRNA+ | Picornavirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C3 | Virus, (animals) | PA (chymotrypsin fold) | IPR044067 | Polyprotein |
ssRNA+ | Patatavirales | ![]() |
Self-cleavage N-ter polyprotein | Cysteine | Peptidase C6 | Virus | CA (Papain fold) | IPR001456 | Polyprotein, HC-pro |
ssRNA+ | Patatavirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C4 | Virus | PA (chymotrypsin fold) | IPR001730 | Polyprotein, Nla-pro |
ssRNA+ | Amarillovirales | ![]() |
Self cleavage N-ter polyprotein | Cysteine | Peptidase C18 | Virus | CM | IPR002518 | Polyprotein, ns2 |
ssRNA+ | Amarillovirales | ![]() |
Self-cleavage N-ter polyprotein, host innate immune response inhibition | Cysteine | Peptidase C53 | Virus | CQ | IPR008751 | Polyprotein, Nterm-pro |
ssRNA+ | Amarillovirales | ![]() |
Self-cleavage N-ter polyprotein | Cysteine | Peptidase C74 | Virus | PA (chymotrypsin fold) | IPR022120 | Polyprotein, ns2 |
ssRNA+ | Tymovirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C21 | Virus | CA (Papain fold) | IPR043181 | Polyprotein |
ssRNA+ | Tymovirales | ![]() |
Polyprotein major protease | Cysteine | Peptidase C23 | Virus | Unassigned | IPR008041 | Polyprotein |
ssRNA+ | Durnavirales | ![]() |
Self cleavage N-ter, Host immune response inhibition | Cysteine | Peptidase C7 | Virus | unassigned | IPR002704 | Papain-like protease p29 |
ssRNA+ | Durnavirales | ![]() |
Self cleavage N-ter, Host immune response inhibition | Cysteine | Peptidase C8 | Virus | unassigned | IPR005315 | Papain-like protease p48 |
dsDNA | Caudoviricetes | ![]() |
Virion maturation | Cysteine | Peptidase C40 | Fungi, bacteria, archaea, virus | CO (Papain fold) | IPR000064 | Tail tip assembly protein K |
dsDNA | Caudoviricetes | ![]() |
Virion maturation | Serine | Peptidase S73 | Fungi, bacteria, archaea, virus | SH | IPR009228 | Capsid assembly scaffolding protein |
dsDNA | Caudoviricetes | ![]() |
Host cell lysis | Cysteine | Peptidase C71 | Virus | CA (Papain fold) | IPR022119 | Pseudomurein endoisopeptidase |
dsDNA | Caudoviricetes | ![]() |
Host cell lysis | Cysteine | Peptidase C51 | Animals, bacteria, archaea, virus | CA (Papain fold) | IPR007921 | Tail lysozyme |
dsDNA | Caudoviricetes | ![]() |
Unknown | Cysteine | Peptidase C51 | Animals, bacteria, archaea, virus | CA (Papain fold) | IPR007921 | Peptidase |
dsDNA | Caudoviricetes | ![]() |
Host cell lysis | Cysteine | Peptidase C51 | Animals, bacteria, archaea, virus | CA (Papain fold) | IPR007921 | Endolysin |
dsDNA | Caudoviricetes | ![]() |
Host cell lysis? | Cysteine | Peptidase C51 | Animals, bacteria, archaea, virus | CA (Papain fold) | IPR007921 | Peptidase |
dsDNA | Herpesvirales | ![]() |
Virion maturation | Serine | Peptidase S21 | Virus, (animals) | SH | IPR001847 | Assemblin |
dsDNA | Herpesvirales | ![]() |
Unknown | Serine | Peptidase S8/S53 | Animals, plant, protozoa, bacteria, archaea, virus | subtilisin SB | IPR036852 | Subtilisin-like |
dsDNA | Herpesvirales | ![]() |
Host cell cycle modulation | Serine | Peptidase C76 | Virus | CA (Papain fold) | IPR006928 | Large tegument protein deneddylase |
dsDNA | Lefavirales | ![]() |
Unknown | Serine | Peptidase S1 | Animals, plant, protozoa, bacteria, archaea, virus | PA (chymotrypsin fold) | IPR001314 | Protease |
dsDNA | Imitervirales | ![]() |
Unknown | Serine | Peptidase S54 | Animals, plant, protozoa, bacteria, archaea, virus | ST | IPR022764 | L523 |
dsDNA | Imitervirales | ![]() |
Unknown | Serine | Peptidase S16 | Animals, plant, protozoa, bacteria, archaea, virus | SJ | IPR027065 | Protease |
dsDNA | Algavirales | ![]() |
Unknown | Serine | Peptidase S74 | Animals, bacteria, archaea, virus | SO | IPR030392 | Protease |
dsDNA | Priklausovirales | ![]() |
unknown | Serine | Peptidase S74 | Animals, bacteria, archaea, virus | SO | IPR030392 | Protease |
dsDNA | Pimascovirales | ![]() |
Unknown | Serine | Peptidase S74 | Animals, bacteria, archaea, virus | SO | IPR030392 | Protease |
dsDNA | Caudovirales | ![]() |
Unknown | Serine | Peptidase S74 | Animals, bacteria, archaea, virus | SO | IPR030392 | Protease |
dsDNA | Caudoviricetes | ![]() |
Virion maturation | Serine | Peptidase S80 | Virus | SH | IPR045405 | Protease |
dsDNA | Caudoviricetes | ![]() |
Virion maturation | Serine | Peptidase S77 | Virus, (plant, bacteria, archaea) | SH | IPR005082 | Prohead core protease |
dsDNA | Caudoviricetes | ![]() |
Virion maturation | Serine | Peptidase S77 | Virus, (plant, bacteria, archaea) | SH | IPR005082 | Prohead core protease |
dsDNA | Caudoviricetes | ![]() |
Virion maturation | Serine | Peptidase S77 | Virus, (plant, bacteria, archaea) | SH | IPR005082 | Prohead core protease |
dsDNA | Caudoviricetes | ![]() |
Virion maturation | Serine | Peptidase S78 | Virus, (plant, bacteria, archaea) | SH | IPR006433 | Prohead core protease |
dsDNA | Caudoviricetes | ![]() |
Virion maturation | Serine | Peptidase S77 | Virus, (plant, bacteria, archaea) | SH | IPR005082 | Prohead core protease |
dsDNA | Caudoviricetes | ![]() |
Virion maturation | Serine | Peptidase S49 | Animals, plant, protozoa, bacteria, archaea, virus | SK | IPR002142 | Prohead core protease |
dsDNA | Caudoviricetes | ![]() |
Unknown | Serine | Peptidase S24 | Animals, plant, protozoa, bacteria, archaea, virus | SF | IPR000129 | Protease |
dsDNA | unassigned | ![]() |
Virion maturation | Serine | Peptidase S50 | Virus, (bacteria) | SJ | IPR002664 | Virion maturation |
dsDNA | Caudoviricetes | ![]() |
Unknown | Serine | Peptidase S74 | Animals, bacteria, virus | SO | PF13884 | Tail fiber protease |
ssRNA+ | Amarillovirales | ![]() |
Polyprotein major protease | Serine | Peptidase S29 | Virus | PA (chymotrypsin fold) | IPR004109 | NS3 |
ssRNA+ | Amarillovirales | ![]() |
Polyprotein major protease | Serine | Peptidase S7 | Virus, (animals, bacteria) | PA (chymotrypsin fold) | IPR001850 | NS3 |
ssRNA+ | Amarillovirales | ![]() ![]() |
Polyprotein major protease | Serine | Peptidase S31 | Virus | PA (chymotrypsin fold) | IPR000280 | NS3 |
ssRNA+ | Nidovirales | ![]() |
Polyprotein major protease | Serine | Peptidase S32 | Virus | PA (chymotrypsin fold) | IPR008760 | NSP4 |
ssRNA+ | Nidovirales | ![]() ![]() |
Polyprotein major protease | Serine | Peptidase S65 | Virus | PA (chymotrypsin fold) | IPR009003 | Polyprotein 1ab |
ssRNA+ | Nidovirales | ![]() ![]() |
Polyprotein major protease | Serine | Peptidase S75 | Virus | PA (chymotrypsin fold) | IPR009003 | Polyprotein 1ab |
ssRNA+ | Sobelivirales | ![]() |
Unknown | Serine | unknown | Virus | |||
ssRNA+ | Sobelivirales | ![]() |
Polyprotein major protease | Serine | Peptidase S39 | Virus | PA (chymotrypsin fold) | IPR000382 | Polyprotein |
ssRNA+ | Sobelivirales | ![]() |
Polyprotein major protease | Serine | Peptidase S39 | Virus | PA (chymotrypsin fold) | IPR000382 | ORF2 |
ssRNA+ | Stellavirales | ![]() |
Polyprotein major protease | Serine | Peptidase PA | Virus | PA (chymotrypsin fold) | IPR009003 | Polyprotein |
ssRNA+ | Patatavirales | ![]() |
Self-cleavage N-ter polyprotein | Serine | Peptidase S30 | Virus | PA (chymotrypsin fold) | IPR002540 | P1 proteinase |
ssRNA+ | Martellivirales | ![]() |
Self-cleavage Nter-POLS | Serine | Peptidase S3 | Virus | PA (chymotrypsin fold) | IPR000930 | Capsid |
ssRNA- | Bunyavirales | ![]() |
Deubiquitinylating Peptidase | Cysteine | Peptidase C87 | Virus | CA (Papain fold) | IPR003323 | L |
Hepatitis E Virus Cysteine Protease Has Papain Like Properties Validated by in silico Modeling and Cell-Free Inhibition Assays
Shweta Saraswat, Meenakshi Chaudhary, Deepak Sehgal
Front Cell Infect Microbiol. 2020 Jan 23;9:478.