Electron Microscopy
2.08Å resolution

Cryo-EM structure of SARS-CoV-2 ORF3a


Function and Biology Details

Reactions catalysed:
(R)-2-hydroxyglutarate + NAD(+) = 2-oxoglutarate + NADH
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
Acyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = 3-oxoacyl-[acyl-carrier-protein] + CO(2) + [acyl-carrier-protein]
Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone
Selective hydrolysis of -Xaa-Xaa-|-Yaa- bonds in which each of the Xaa can be either Arg or Lys and Yaa can be either Ser or Ala.
D-galactose + O(2) = D-galacto-hexodialdose + H(2)O(2)
Hydrolysis of terminal non-reducing alpha-L-arabinofuranoside residues in alpha-L-arabinosides
Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates.
Hydrolysis of proteins to small peptides in the presence of ATP and magnesium. Alpha-Casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are hydrolyzed (such as succinyl-Leu-Tyr-|-NHMec; and Leu-Tyr-Leu-|-Tyr-Trp, in which cleavage of the -Tyr-|-Leu- and -Tyr-|-Trp bonds also occurs).
3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid
ATP + protein L-histidine = ADP + protein N-phospho-L-histidine
CoA-(4'-phosphopantetheine) + apo-[acyl-carrier-protein] = adenosine 3',5'-bisphosphate + holo-[acyl-carrier-protein]
Acts on substrates that are at least partially unfolded. The cleavage site P1 residue is normally between a pair of hydrophobic residues, such as Val-|-Val
Peptidylproline (omega=180) = peptidylproline (omega=0)
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)
Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.
Autocatalytically cleaves itself from the polyprotein of the foot-and-mouth disease virus by hydrolysis of a Lys-|-Gly bond, but then cleaves host cell initiation factor eIF-4G at bonds -Gly-|-Arg- and -Lys-|-Arg-.
Nitric oxide + H(2)O + ferricytochrome c = nitrite + ferrocytochrome c + 2 H(+)
ATP + a protein = ADP + a phosphoprotein
NH(3) + 2 H(2)O + 6 ferricytochrome c = nitrite + 6 ferrocytochrome c + 7 H(+)
Beta-D-ribopyranose = beta-D-ribofuranose
D-glucarate = 5-dehydro-4-deoxy-D-glucarate + H(2)O
(R)-10-hydroxystearate = oleate + H(2)O
NTP + H(2)O = NDP + phosphate
GTP + a 5'-diphospho-[mRNA] = diphosphate + a 5'-(5'-triphosphoguanosine)-[mRNA]
N-acetyl-O-acetylneuraminate + H(2)O = N-acetylneuraminate + acetate
An aldehyde + NAD(P)(+) + H(2)O = a carboxylate + NAD(P)H
Selective cleavage of Tyr-|-Gly bond in picornavirus polyprotein.
(S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate = fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
S-adenosyl-L-methionine + a 5'-(5'-triphosphoguanosine)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA]
Pyridoxamine 5'-phosphate + H(2)O + O(2) = pyridoxal 5'-phosphate + NH(3) + H(2)O(2)
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate = diphosphate + geranylgeranyl diphosphate
Release of N-terminal proline from a peptide.
Release of an N-terminal amino acid, Xaa-|-Yaa-, in which Xaa is preferably Leu, but may be other amino acids including Pro although not Arg or Lys, and Yaa may be Pro. Amino acid amides and methyl esters are also readily hydrolyzed, but rates on arylamides are exceedingly low.
L-histidinol phosphate + H(2)O = L-histidinol + phosphate
Succinate semialdehyde + NADP(+) + H(2)O = succinate + NADPH
Cellobiose = 4-O-beta-D-glucopyranosyl-D-mannose
N(2)-acetyl-L-ornithine + L-glutamate = L-ornithine + N-acetyl-L-glutamate
3-phospho-D-glycerate + NAD(+) = 3-phosphonooxypyruvate + NADH
Isochorismate + H(2)O = (2S,3S)-2,3-dihydroxy-2,3-dihydrobenzoate + pyruvate
ATP + H(2)O + a folded polypeptide = ADP + phosphate + an unfolded polypeptide
Preferential cleavage: (Ac)(2)-L-Lys-D-Ala-|-D-Ala. Also transpeptidation of peptidyl-alanyl moieties that are N-acyl substituents of D-alanine.
Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
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.
L-lysine + NADPH + O(2) = N(6)-hydroxy-L-lysine + NADP(+) + H(2)O
Hydrolysis of terminal non-reducing beta-D-galactose residues in beta-D-galactosides
5-hydroxyisourate + H(2)O = 5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
Cutin + H(2)O = cutin monomers
ATP + H(2)O = ADP + phosphate
Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.
4 Fe(2+) + 4 H(+) + O(2) = 4 Fe(3+) + 2 H(2)O
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
Geranylgeranyl diphosphate = (+)-copalyl diphosphate
(GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala))(n)-diphosphoundecaprenol + GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol = (GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala))(n+1)-diphosphoundecaprenol + undecaprenyl diphosphate
A beta-lactam + H(2)O = a substituted beta-amino acid
The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate
Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
S-adenosyl-L-methionine + uracil(1498) in 16S rRNA = S-adenosyl-L-homocysteine + N(3)-methyluracil(1498) in 16S rRNA 
L-cystathionine + H(2)O = L-homocysteine + NH(3) + pyruvate
(1a) L-cystathionine = L-cysteine + 2-aminobut-2-enoate
(S)-3-hydroxyacyl-CoA + NAD(+) = 3-oxoacyl-CoA + NADH
L-arginine + 2-oxoglutarate + O(2) = (3S)-3-hydroxy-L-arginine + succinate + CO(2)
Hydrolyzes poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
(1a) [acetyl-CoA C-acyltransferase]-S-acyl-L-cyteine + acetyl-CoA = 3-oxoacyl-CoA + [acetyl-CoA C-acyltransferase]-L-cyteine
ATP + glycerol = ADP + sn-glycerol 3-phosphate
L-homoserine + NAD(P)(+) = L-aspartate 4-semialdehyde + NAD(P)H
Diphosphate + H(2)O = 2 phosphate
An aldehyde + H(2)O + 2 oxidized ferredoxin = a carboxylate + 2 H(+) + 2 reduced ferredoxin
N-carbamoylputrescine + H(2)O = putrescine + CO(2) + NH(3)
ATP + acetyl-CoA + HCO(3)(-) = ADP + phosphate + malonyl-CoA
ATP + propanoyl-CoA + HCO(3)(-) = ADP + phosphate + (S)-methylmalonyl-CoA
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
D-fructose 1,6-bisphosphate + H(2)O = D-fructose 6-phosphate + phosphate
Cleaves -Ala-|-Ser- and -Ala-|-Ala- bonds in the scaffold protein.
TSAVLQ-|-SGFRK-NH(2) and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
ATP + H(2)O + 4 H(+)(Side 1) = ADP + phosphate + 4 H(+)(Side 2)
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin
Biochemical function:
Cellular component:

Structure analysis Details

Assembly composition:
hetero tetramer (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
ORF3a protein Chains: A, B
Molecule details ›
Chains: A, B
Length: 284 amino acids
Theoretical weight: 32.17 KDa
Source organism: Severe acute respiratory syndrome coronavirus 2
Expression system: Spodoptera frugiperda
  • Canonical: P0DTC3 (Residues: 1-275; Coverage: 100%)
Gene name: 3a
Sequence domains: Betacoronavirus viroporin
Truncated apolipoprotein A-I Chains: C, D
Molecule details ›
Chains: C, D
Length: 210 amino acids
Theoretical weight: 24.65 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
  • Canonical: P02647 (Residues: 79-267; Coverage: 76%)
Gene name: APOA1

Ligands and Environments

1 bound ligand:
No modified residues

Experiments and Validation Details

Entry percentile scores
Resolution: 2.08Å
Relevant EMDB volumes: EMD-22898
Expression systems:
  • Spodoptera frugiperda
  • Escherichia coli