3.4.22.B50 malfunction arteriviruses lacking PLP2 deubiquitinase activity elicit an enhanced host innate immune response 732827 3.4.22.B50 malfunction mutations of residues in the enzyme-ubiquitin interface lead to reduced catalytic activity 731069 3.4.22.B50 additional information enzyme structure and function, active site structure with catalytic triad residues, Cys112, His273 and Asp287 and the oxyanion hole-stabilizing residue Trp107, and catalytic mechanism, detailed overview. The fingers domain of PLpro, which contains a zinc ion that is tetrahedrally coordinated by four cysteines, is essential for catalysis because it maintains the structural integrity of the enzyme 731149 3.4.22.B50 additional information the enzyme comprises the viral polyprotein residues 1541-1858 731069 3.4.22.B50 physiological function changes within the Ubl domain, residues 785 to 787 of nonstructural protein 3, negatively affect protease activity. Ubl mutant viruses V787S and V785S replicate efficiently at 37°C but generate smaller plaques than wild-type virus, and V787S is defective for replication at higher temperatures. The proteases of the mutant viruses exhibit similar specific activities at 25°C but diplay significantly reduced thermal stability at 30°C, thereby reducing the total enzymatic activity. Infection of C57BL/6 mice with V787S is highly attenuated, yet it replicates sufficiently to elicit protective immunity 754545 3.4.22.B50 physiological function papain-like protease domain 2 (PLP2) deubiquitinates TANK-binding kinase-1 (TBK1) and reduces its kinase activity, hence inhibits interferon-beta reporter activity and prevents interferon regulatory factor 3 (IRF3) nuclear translocation. The presence of PLP2 stabilizes the hypo-phosphorylated IRF3-TBK1 complex in a dose-dependent manner in the cytoplasm 718275 3.4.22.B50 physiological function PLP2 is responsible for the inhibition of both RIG-I and TLR3-dependent induction of interferon alpha/beta expression 718347 3.4.22.B50 physiological function the enzyme is essential for arterivirus replication by cleaving a site within the viral replicase polyproteins and also removes ubiquitin from cellular proteins. This deubiquitinase activity is a critical factor in arteriviral innate immune evasion 732827 3.4.22.B50 physiological function the enzyme is one of two cysteine proteases involved in the proteolytic processing of the polyproteins of Severe acute respiratory syndrome coronavirus. It also shows significant in vitro deubiquitinating and de-ISGylating activities 731069 3.4.22.B50 physiological function the enzyme strongly inhibits RIG-Iand STING-activated interferon expression. Papain-like protease 2 acts as a viral deubiquitinase to interfere with the RIG-I- and STING-mediated signalling pathway 732257 3.4.22.B50 physiological function the primary function of the enzyme is to process the viral polyprotein in a coordinated manner. An additional function of the enzyme is stripping ubiquitin and ISG15 from host-cell proteins to aid the coronavirus in the evasion of the host innate immune responses, enzyme innate immune functions, overview 731149