Literature summary for 3.4.21.91 extracted from

Li, Y.; Zhang, Z.; Phoo, W.W.; Loh, Y.R.; Li, R.; Yang, H.Y.; Jansson, A.E.; Hill, J.; Keller, T.H.; Nacro, K.; Luo, D.; Kang, C.
Structural insights into the inhibition of Zika virus NS2B-NS3 protease by a small-molecule inhibitor (2018), Structure, 26, 555-564.e3 .

Search for more literature for 3.4.21.91

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified bZiPro (C143S)-inhibitor 5-amino-1-((4-methoxyphenyl)sulfonyl)-1H-pyrazol-3-yl benzoate complex and bZiPro (C143S)-Ac-Lys-Arg complex, X-ray diffraction structure determination and analysis at 1.90 A and 1.51 A resolution, respectively	Zika virus

Protein Variants

Protein Variants	Comment	Organism
C143S	site-directed mutagenesis, the NS2B mutant cannot form the disulfide bond between C143 residues of neighboring NS3	Zika virus

Inhibitors

Inhibitors	Comment	Organism	Structure
5-amino-1-((4-methoxyphenyl)sulfonyl)-1H-pyrazol-3-ol	-	Zika virus
5-amino-1-((4-methoxyphenyl)sulfonyl)-1H-pyrazol-3-yl benzoate	the benzoyl moiety of the inhibitor forms a covalent bond with the side chain of S135. Structure and dynamics of bZiPro-inhibitor complex in solution	Zika virus
additional information	structural insights into the inhibition of Zika virus NS2B-NS3 protease by a small-molecule inhibitor, structure and dynamics, overview. 5-amino-1-((4-methoxyphenyl)sulfonyl)-1H-pyrazol-3-yl benzoate stabilizes the closed conformation of ZIKV protease. Upon hydrolysis in situ into two fragments, the benzoyl group of the inhibitor forms a covalent bond with the side chain of catalytic residue S135, whereas the second fragment exhibits no obvious molecular interactions with the protease, detailed mechanism of action of a covalent inhibitor. Unique adduct of the benzoyl moiety to residue S135	Zika virus

Organism

Organism	UniProt	Comment	Textmining
Zika virus	-	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
benzoyl-Nle-Lys-Arg-Arg-7-amido-4-methylcoumarin + H2O	-	Zika virus	benzoyl-Nle-Lys-Arg-Arg + 7-amino-4-methylcoumarin	-	?

Subunits

Subunits	Comment	Organism
dimer	Zika protease is able to form a dimer, and a disulfide bond between C143 residues of neighboring NS3 in the crystal is observed	Zika virus

Synonyms

Synonyms	Comment	Organism
NS2B-NS3 protease	-	Zika virus
Zika protease	-	Zika virus
Zika virus NS2B-NS3 protease	-	Zika virus

Cofactor

Cofactor	Comment	Organism	Structure
NS2B cofactor	the viral protease is a two-component serine protease formed by the N-terminal part of NS3 and the cofactor region of NS2B, a membrane protein essential for the membrane location of NS3. The NS2B mutant C143S cannot form the disulfide bond between C143 residues of neighboring NS3	Zika virus

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.0015	-	20xa0mM Tris pH 8.5, 10% glycerol, 0.01% Triton X-100, 37°C	Zika virus	5-amino-1-((4-methoxyphenyl)sulfonyl)-1H-pyrazol-3-yl benzoate

General Information

General Information	Comment	Organism
additional information	the viral protease is a two-component serine protease formed by the N-terminal part of NS3 and the cofactor region of NS2B, a membrane protein essential for the membrane location of NS3	Zika virus

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Release 2023.1 (January 2023)