Literature summary for 3.4.21.113 extracted from

Zheng, F.; Lu, G.; Li, L.; Gong, P.; Pan, Z.
Uncoupling of protease trans-cleavage and helicase activities in pestivirus NS3 (2017), J. Virol., 91, e01094-17 .

Search for more literature for 3.4.21.113

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified full-length CSFV NS3 with its NS4A PCS covalently tethered to its N terminus through a flexible linker, X-ray diffraction structure determination and analysis at 2.35 A resolution	Classical swine fever virus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
additional information	Classical swine fever virus	the enzyme is a natural protease-helicase fusion protein, structure-function analysis, overview	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Classical swine fever virus	Q5U8X5	CSFV, a pestivirus	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
proteolytic modification	the viral RNA genome contains one large open reading frame (ORF) encoding a polyprotein of about 4,000 amino acids. The polyprotein is co- and posttranslationally processed into at least 12 mature proteins by viral and host proteases through cis (intramolecular) or trans (intermolecular) mechanisms. Core, Erns, E1, and E2 are the structural proteins that become part of the mature virion, and the eight nonstructural proteins Npro, p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B are involved in polyprotein processing, viral genome replication, and virus morphogenesis. cis-Cleavage events are essential to generate structurally independent proteases that may carry out trans-cleavages more efficiently than proteases in the form of polyprotein. Limitations are also applied to cis-cleavages, as the intramolecular recognition of the cleavage site requires the protease protein to adopt certain conformations that may not always achievable. Two minor autocleavage sites, Leu192/Met193 and Leu159/Lys160, are detected within the NS3 protease module	Classical swine fever virus

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	the enzyme is a natural protease-helicase fusion protein, structure-function analysis, overview	Classical swine fever virus	?	-	?
additional information	the S1 pocket of the active site to accommodate the P1 residue (i.e., the immediate N-terminal residue of the cleavage site) is relatively deep and small, with a primarily hydrophobic environment, similar to the S1 pocket of HCV NS3. In contrast, the flavivirus NS3 P1 site is relatively flat and spacious but not as hydrophobic, substrate specificity, overview	Classical swine fever virus	?	-	?

Subunits

Subunits	Comment	Organism
More	the NS3-NS4APCS protease contains a typical dual beta-barrel core observed in the chymotrypsin-like serine proteases, and the PCS participates in the folding of both the N- and C-terminal barrels (N-barrel and C-barrel). The N-terminal 14 residues intertwine with NS4A residues 29 to 41 to form a long anti-parallel beta-type structural element that bridges the N- and C-barrels of the protease. NS3 protease protein structure comparisons, overview	Classical swine fever virus

Synonyms

Synonyms	Comment	Organism
CSFV NS3	-	Classical swine fever virus
pestivirus NS3 protease	-	Classical swine fever virus

General Information

General Information	Comment	Organism
evolution	comparison of the Flaviviridae NS3 proteases	Classical swine fever virus
malfunction	altering either of the autocleavage sites (Leu192/Met193 and Leu159/Lys160) by Leu deletion or mutation greatly inhibits RNA replication in a CSFV replicon system and results in a loss of genome RNA infectivity	Classical swine fever virus
additional information	the catalytic triad is formed by residues H69, D97, and S163. The intramolecular interface between protease and helicase in CSFV NS3 is featured by three clusters of interactions, overview	Classical swine fever virus
physiological function	NS3 is a multifunctional enzyme and a natural fusion of an N-terminal chymotrypsin-like serine protease and a C-terminal nucleotide triphosphatase (NTPase)/helicase. All Flaviviridae NS3 proteases require a segment of another viral protein, NS4A for pestiviruses, as the structurally integrated essential cofactor, termed protease cofactor segment (PCS) to fulfill the protease function, and for pestiviruses the protease is responsible for the cleavage of all the linkages in the NS3-NS4A-NS4B-NS5A-NS5B region of the viral polyprotein. The enzyme is a natural protease-helicase fusion protein, structure-function analysis, overview. Analysis of the mechanism of NS3 helicase regulation by its fusion partner protease	Classical swine fever virus

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Release 2023.1 (January 2023)