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Function
The organism PLpro is from is Coronaviruses. IBV PLpro performs deubiquitination with catalytic efficiencies that are different from other PLpros. Papain-like protease (PLpro) of coronaviruses (CoVs) carries out proteolytic maturation of non-structural proteins that play a role in replication of the virus and performs deubiquitination of host cell factors to scuttle antiviral responses. This action blocks the activation
of host antiviral signaling pathway. The substrates and products are PLpro and ubiquitin.
Disease
A disease associated with the protein is avian infectious bronchitis in poultry. The protein helps out with scuttling antiviral responses and when this protein is working it stops the host(chicken) from being able to keep the virus from replicating. Other diseases associated with PLpro include respiratory tract infections and uro-gential tract infections.
Relevance
The avian infectious bronchitis virus, IBV, causes bronchitis in chickens and results in huge economic losses every year in the poultry business, and it encodes a PLpro. Understanding how this protein works in the body can help us figure out how to fight this virus and stop the huge loss of chickens each year. The results from this can help provide a way to create antivirals for not only this virus but others as well. Since ubiquitination is not limited to immune responses, PLpros are probably capable of modulating other aspects of the host cell regulated by ubiquitination meaning their impact on the cells goes beyond just this and should be explored further.
Structural highlights
Here is a of PLpro, it's main secondary features are mainly beta sheets and with alpha helixes and a little less random coils.
In this the most important tertiary and quaternary structures of PLpro are highlighted. They include the P4 residues which is the resides that the most impact on catalytic efficiency.
This is a view of PLpro where it shows how much space the atoms take up in the protein.
Here is a of PLpro, the importance of hydrophobic and hydrophilic regions are that they determine how the proteins fold and that is the case in PLpro as well. PLpro has a mix of hydrophobic and hydrophilic regions.
Here is a view of the . The important chemical features of the ligand is that they form H bonds with each other and have metal interactions with Zinc. The amino acids that interact with the ligand are Cystine, Threonine and Arginine. Cystine interacts with Zn through metal interactions as well as forms H bonds with other Cystines and Threonine.
This is the and it helps the protein achieve its function by helping the protein reveal key differences in substrate binding sites of PLpros. Specifically the P3 and P4 sub sites and the residues that interact with the-barrel of ubiquitin are different. This suggest a difference in catalytic activity. It helps the protein function more efficiently by revealing and opening up different binding sites. The catalytic triad include D275, H264, C101.
The is pictured here and has the key amino acids highlighted. Those key amino acids are W156, D223, N155 and IIe. W156 is involved in shaping the S2 subsite for a glycine, D223 and N155 help form the pocket and shape active site. IIe replaces T302 which obstructs the placement of the side chain of lysine residue causing BL1 to be moved creating a larger pocket.
Additional structural features include the region around , the the region between the of the PLpro that binds the beta barrel of ubiquitin or the viral peptide substrate, and the region behind that holds the part of the peptide downstream of the cleavage site. These regions are important because they govern the substrate selection.
Kinetic Data
This article compares the kinetic parameters of PLpros from different COVs. Sars COV followed by IBV had higher catalytic efficiencies than MERS COV. This information helps tell us what the proteins can cleave at a given catalytic efficiency. This allows them to see the relationship between the two and see at what catalytic efficiency can the protein still operate and function properly.
