DB code: M00209

RLCP classification 1.13.30000.46 : Hydrolysis
CATH domain 2.60.120.20 : Jelly Rolls
2.60.120.20 : Jelly Rolls
-.-.-.- :
-.-.-.- :
-.-.-.- :
2.40.10.10 : Thrombin, subunit H Catalytic domain
2.40.10.10 : Thrombin, subunit H Catalytic domain
-.-.-.- :
4.10.880.10 : Poliovirus 3D polymerase; domain 1 (Nucleotidyltransferase)
3.30.70.270 : Alpha-Beta Plaits
1.20.960.20 : Mitochondrial Import Receptor Subunit Tom20; Chain A
E.C. 3.6.1.15 3.4.22.28 2.7.7.48
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.40.10.10 : Thrombin, subunit H M00139 D00214 M00167 D00426 M00133 D00428 D00429 D00430 D00431 D00432 D00433 D00434 D00435 M00227 D00194 D00197 D00211 D00212 D00216 M00212 D00224 D00497 M00217 M00216 D00528 D00848 D00850 D00851 D00852 D00855 M00152 M00155 M00157 M00181 M00315 M00316 M00317 M00348 M00349 T00074 T00410 T00411
3.30.70.270 : Alpha-Beta Plaits M00206 M00019 M00135 M00146 M00166

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq Pfam
P08617 Genome polyprotein
None Protein VP0 VP4-VP2
Protein VP4 P1A Virion protein 4
Protein VP2 P1B Virion protein 2
Protein VP3 P1C Virion protein 3
Protein VP1-2A PX
Protein VP1 P1D Virion protein 1
Protein 2A
(P2A)
Protein 2BC
Protein 2B
(P2B)
Protein 2C
(P2C)
EC 3.6.1.15
Protein 3ABCD
(P3)
Protein 3ABC
Protein 3AB
Protein 3A
(P3A)
Protein 3B
(P3B)
VPg
Protein 3CD
Protease 3C
(P3C)
EC 3.4.22.28
Picornain 3C
RNA-directed RNA polymerase 3D-POL
(P3D-POL)
EC 2.7.7.48
NP_041007.1 (Protein)
NC_001489.1 (DNA/RNA sequence)
NP_041008.1 (Protein)
NC_001489.1 (DNA/RNA sequence)
PF12944 (DUF3840)
PF00548 (Peptidase_C3)
PF00680 (RdRP_1)
PF00073 (Rhv)
PF00910 (RNA_helicase)
[Graphical View]

KEGG enzyme name
nucleoside-triphosphatase
(EC 3.6.1.15 )
nucleoside triphosphate phosphohydrolase
(EC 3.6.1.15 )
nucleoside-5-triphosphate phosphohydrolase
(EC 3.6.1.15 )
nucleoside 5-triphosphatase
(EC 3.6.1.15 )
picornain 3C
(EC 3.4.22.28 )
picornavirus endopeptidase 3C
(EC 3.4.22.28 )
poliovirus protease 3C
(EC 3.4.22.28 )
rhinovirus protease 3C
(EC 3.4.22.28 )
foot-and-mouth protease 3C
(EC 3.4.22.28 )
poliovirus proteinase 3C
(EC 3.4.22.28 )
rhinovirus proteinase 3C
(EC 3.4.22.28 )
coxsackievirus 3C proteinase
(EC 3.4.22.28 )
foot-and-mouth-disease virus proteinase 3C
(EC 3.4.22.28 )
3C protease
(EC 3.4.22.28 )
3C proteinase
(EC 3.4.22.28 )
cysteine proteinase 3C
(EC 3.4.22.28 )
hepatitis A virus 3C proteinase
(EC 3.4.22.28 )
protease 3C
(EC 3.4.22.28 )
tomato ringspot nepovirus 3C-related protease
(EC 3.4.22.28 )
RNA-directed RNA polymerase
(EC 2.7.7.48 )
RNA nucleotidyltransferase (RNA-directed)
(EC 2.7.7.48 )
RNA nucleotidyltransferase (RNA-directed)
(EC 2.7.7.48 )
RNA-dependent ribonucleate nucleotidyltransferase
(EC 2.7.7.48 )
3D polymerase
(EC 2.7.7.48 )
PB1 proteins
(EC 2.7.7.48 )
PB2 proteins
(EC 2.7.7.48 )
phage f2 replicase
(EC 2.7.7.48 )
polymerase L
(EC 2.7.7.48 )
Q-beta replicase
(EC 2.7.7.48 )
phage f2 replicase
(EC 2.7.7.48 )
ribonucleic acid replicase
(EC 2.7.7.48 )
ribonucleic acid-dependent ribonucleate nucleotidyltransferase
(EC 2.7.7.48 )
ribonucleic acid-dependent ribonucleic acid polymerase
(EC 2.7.7.48 )
ribonucleic replicase
(EC 2.7.7.48 )
ribonucleic synthetase
(EC 2.7.7.48 )
RNA replicase
(EC 2.7.7.48 )
RNA synthetase
(EC 2.7.7.48 )
RNA transcriptase
(EC 2.7.7.48 )
RNA-dependent ribonucleate nucleotidyltransferase
(EC 2.7.7.48 )
RDRP
(EC 2.7.7.48 )
RNA-dependent RNA polymerase
(EC 2.7.7.48 )
RNA-dependent RNA replicase
(EC 2.7.7.48 )
transcriptase
(EC 2.7.7.48 )

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P08617 POLG_HAVHM Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1). Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly. NTP + H(2)O = NDP + phosphate. 3AB precursor is a homodimer. 3AB precursor interacts with 3CD precursor. Protein 3ABC interacts with human MAVS. Protein VP2: Virion. Cytoplasm (Potential). Protein VP3: Virion. Cytoplasm (Potential). Protein VP1: Virion. Cytoplasm (Potential). Protein VP1-2A: Virion. Cytoplasm (Potential). Protein 2B: Cytoplasmic vesicle membrane, Peripheral membrane protein, Cytoplasmic side (Potential). Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum. Protein 2C: Cytoplasmic vesicle membrane, Peripheral membrane protein, Cytoplasmic side (Potential). Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum. May associate with membranes through a N- terminal amphipathic helix. Protein 3ABC: Cytoplasmic vesicle membrane, Peripheral membrane protein, Cytoplasmic side (Potential). Mitochondrion outer membrane, Peripheral membrane protein, Cytoplasmic side (Potential). Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum. Protein 3AB: Cytoplasmic vesicle membrane, Peripheral membrane protein, Cytoplasmic side (Potential). Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum. Protein 3A: Cytoplasmic vesicle membrane, Peripheral membrane protein, Cytoplasmic side (Potential). Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum. Protein 3B: Virion (Potential). Picornain 3C: Cytoplasm (Potential). RNA-directed RNA polymerase 3D-POL: Cytoplasmic vesicle membrane, Peripheral membrane protein, Cytoplasmic side (Potential). Note=Interacts with membranes in a complex with viral protein 3AB. Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.

KEGG Pathways
Map code Pathways E.C.
MAP00730 Thiamine metabolism 3.6.1.15
MAP00230 Purine metabolism 3.6.1.15 2.7.7.48

Compound table
Substrates Products Intermediates
KEGG-id C00201 C00017 C00001 C00046 C00454 C00009 C00017 C00012 C00046 C00013 I00153 I00154 I00155
E.C. 3.6.1.15
2.7.7.48
3.4.22.28
3.6.1.15
3.4.22.28
2.7.7.48
3.6.1.15
3.6.1.15
3.4.22.28
3.4.22.28
2.7.7.48
2.7.7.48
3.4.22.28
3.4.22.28
3.4.22.28
Compound Nucleoside triphosphate Protein H2O RNA(n) Nucleoside diphosphate Phosphate Protein Peptide RNA(n+1) Diphosphate Peptidyl-Cys-tetrahedral-intermediate (with previous peptide) Acyl-enzyme(Peptidyl-Cys-acyl group) Peptidyl-Cys-tetrahedral-intermediate
Type nucleotide peptide/protein H2O nucleic acids nucleotide phosphate group/phosphate ion peptide/protein peptide/protein nucleic acids phosphate group/phosphate ion
ChEBI 15377
26078
29888
PubChem 22247451
962
1004
22486802
1023
21961011
1havA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1havB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1qa7A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1qa7B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1qa7C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1qa7D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1havA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1havB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1qa7A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:IVF Unbound
1qa7B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:IVF Unbound
1qa7C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:IVF Unbound
1qa7D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:IVF Unbound

Reference for Active-site residues
resource references E.C.
PDB;1hav & literature [7]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1havA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 44 mutant C24S
1havB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 44 mutant C24S
1qa7A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 44
1qa7B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 44
1qa7C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 44
1qa7D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 44
1havA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 143;CYS 172 MET 171;CYS 172
1havB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 143;OCS 172 OCS 172(Sulfonic acid) MET 171;OCS 172
1qa7A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 143;CYS 172 MET 171;CYS 172
1qa7B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 143;CYS 172 MET 171;CYS 172
1qa7C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 143;CYS 172 MET 171;CYS 172
1qa7D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 143;CYS 172 MET 171;CYS 172

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
p.75
[7]
p.2440-2442
[9]
p.159

References
[1]
Resource
Comments
Medline ID
PubMed ID 8254682
Journal J Mol Biol
Year 1993
Volume 234
Pages 890-3
Authors Chernaia MM, Malcolm BA, Allaire M, James MN
Title Hepatitis A virus 3C proteinase: some properties, crystallization and preliminary crystallographic characterization.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8071130
Journal J Antibiot (Tokyo)
Year 1994
Volume 47
Pages 836-9
Authors Kadam S, Poddig J, Humphrey P, Karwowski J, Jackson M, Tennent S, Fung L, Hochlowski J, Rasmussen R, McAlpine J
Title Citrinin hydrate and radicinin: human rhinovirus 3C-protease inhibitors discovered in a target-directed microbial screen.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 7664075
Journal Nat Struct Biol
Year 1994
Volume 1
Pages 505-6
Authors Allaire M, James M
Title Deduction of the 3C proteinases' fold.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8164744
Journal Nature
Year 1994
Volume 369
Pages 72-6
Authors Allaire M, Chernaia MM, Malcolm BA, James MN
Title Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 7794931
Journal Biochemistry
Year 1995
Volume 34
Pages 8172-9
Authors Malcolm BA, Lowe C, Shechosky S, McKay RT, Yang CC, Shah VJ, Simon RJ, Vederas JC, Santi DV
Title Peptide aldehyde inhibitors of hepatitis A virus 3C proteinase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9367789
Journal J Mol Biol
Year 1997
Volume 273
Pages 1032-47
Authors Mosimann SC, Cherney MM, Sia S, Plotch S, James MN
Title Refined X-ray crystallographic structure of the poliovirus 3C gene product.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9032381
Journal J Virol
Year 1997
Volume 71
Pages 2436-48
Authors Bergmann EM, Mosimann SC, Chernaia MM, Malcolm BA, James MN
Title The refined crystal structure of the 3C gene product from hepatitis A virus: specific proteinase activity and RNA recognition.
Related PDB 1hav
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10353640
Journal Bioorg Med Chem
Year 1999
Volume 7
Pages 607-19
Authors Huang Y, Malcolm BA, Vederas JC
Title Synthesis and testing of azaglutamine derivatives as inhibitors of hepatitis A virus (HAV) 3C proteinase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10603326
Journal Virology
Year 1999
Volume 265
Pages 153-63
Authors Bergmann EM, Cherney MM, Mckendrick J, Frormann S, Luo C, Malcolm BA, Vederas JC, James MN
Title Crystal structure of an inhibitor complex of the 3C proteinase from hepatitis A virus (HAV) and implications for the polyprotein processing in HAV.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10507325
Journal Virus Res
Year 1999
Volume 62
Pages 159-68
Authors Seipelt J, Guarne A, Bergmann E, James M, Sommergruber W, Fita I, Skern T
Title The structures of picornaviral proteinases.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11256814
Journal J Biomol NMR
Year 2001
Volume 19
Pages 187-8
Authors Bjorndahl TC, Watson MS, Slupsky CM, Spyracopoulos L, Sykes BD, Wishart DS
Title Complete 1H, 13C and 15N backbone assignments for the hepatitis A virus 3C protease.
Related PDB
Related UniProtKB

Comments
The virus proteins (Swiss-prot;P08617, P26582) are composed of four coat proteins, three core proteins, P2A, P2B and P2C (E.C. 3.6.1.15), and three probable proteins, P3A, P3B and P3C, and RNA-directed polymerase 3D (E.C. 2.7.7.48). However, the structures (PDB; 1hav & 1qa7) correspond to the P3C, which seems to be cysteine protease.
This protease belongs to the peptidase family-C3.
According to the literature [7] & [9], Cys172 acts as a nucleophile, whilst His44 serve as a general acid-base. The nucleophilic cysteine and the acid-base histidine form a thiolate-imidazolium ion pair. Moreover, this enzyme has got the electrophilic oxyanion hole, made up by the mainchain of residues 169-172, as observed in chymotrypsin.
Furthermore, the sidechain of Tyr143 is close to a water, which is hydrogen-bonded to His44, and to His44. This residue is considered to be negatively charged (see [7]). Thus, Tyr143 might stabilize a positive charge on the imidazole of His44, to maintain the protonation state of His44.

Created Updated
2003-07-22 2012-10-22