Literature summary for 3.4.21.91 extracted from

Zhu, L.; Yang, J.; Li, H.; Sun, H.; Liu, J.; Wang, J.
Conformational change study of dengue virus NS2B-NS3 protease using 19F NMR spectroscopy (2015), Biochem. Biophys. Res. Commun., 461, 677-680 .

Search for more literature for 3.4.21.91

Application

Application	Comment	Organism
drug development	the dengue virus NS2B-NS3 protease (NS2B-NS3p) is an important antiviral target for drug development	Dengue virus type 2

Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of His-tagged enzyme complex mutant H51A/S75C in Escherichia coli strain BL21(DE3)	Dengue virus type 2

Protein Variants

Protein Variants	Comment	Organism
H51A	site-directed mutagenesis, the mutation of NS3 protein impairs the charge interaction and the pH dependence of the conformational changes. It stabilizes the open conformation, while the addition of BPTI still converts NS2B-NS3p from open to closed conformation	Dengue virus type 2
H51A/S75C	complex mutations	Dengue virus type 2
S75C	site-directed mutagenesis, the mutation of NS2B protein	Dengue virus type 2

Inhibitors

Inhibitors	Comment	Organism	Structure
Bovine pancreatic trypsin inhibitor	BPTI	Dengue virus type 2

Organism

Organism	UniProt	Comment	Textmining
Dengue virus type 2	-	DENV2	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged enzyme complex mutant H51A/S75C from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration	Dengue virus type 2

Synonyms

Synonyms	Comment	Organism
dengue virus NS2B-NS3 protease	-	Dengue virus type 2
NS2B-NS3 protease	-	Dengue virus type 2
NS2B-NS3p	-	Dengue virus type 2

Cofactor

Cofactor	Comment	Organism	Structure
NS2B cofactor	The dengue virus NS2B-NS3 protease (NS2B-NS3p), an important antiviral target for drug development, has been reported to adopt an open or closed conformation in crystal structures with different NS2B C-terminus (NS2Bc) positioning. NS2Bc departs from NS3p in the open conformation, but it forms tight interactions with NS3p in the closed conformation	Dengue virus type 2

General Information

General Information	Comment	Organism
additional information	the enzyme is a complex of NS2B cofactor and NS3 protein. It adopts an open or closed conformation in crystal structures with different NS2B C-terminus (NS2Bc) positioning. In solution, NS2B-NS3p forms a mixture of open, closed and maybe other intermediate conformations. Analysis of the conformational changes using 19F NMR spectroscopy and enzyme mutant H51A/S75C. Low pH or bovine pancreatic trypsin inhibitor (BPTI) binding promote the conformation change from open to closed, showing the importance of charge forces in the interaction between NS2Bc and NS3p. NS3p residue His51 plays a crucial role in the pH-dependent conformational exchange by charge interacting with NS2Bc	Dengue virus type 2

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Release 2023.1 (January 2023)