7tcz | pdb_00007tcz

Human cytomegalovirus protease mutant (C84A, C87A, C138A, C202A) in complex with inhibitor

spinqualitylabelsall models 7tcz, resolution 2.67Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7tcz is a 1 chain structure with sequence from Human betaherpesvirus 5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.67Å Ligands: GIT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SCAF_HCMVA Capsid scaffolding protein acts as a scaffold protein by binding major capsid protein UL86 in the cytoplasm, inducing the nuclear localization of both proteins. Multimerizes in the nucleus such as protein UL86 forms the icosahedral T=16 capsid. Autocatalytic cleavage releases the assembly protein, and subsequently abolishes interaction with major capsid protein UL86. Cleavages products are evicted from the capsid before or during DNA packaging (By similarity). Assemblin is a protease essential for virion assembly in the nucleus. Catalyzes the cleavage of the assembly protein after complete capsid formation. Assemblin and cleavages products are evicted from the capsid before or during DNA packaging (By similarity). Assembly protein plays a major role in capsid assembly. Acts as a scaffold protein by binding major capsid protein UL86. Multimerizes in the nucleus such as protein UL86 forms the icosahedral T=16 capsid. Cleaved by assemblin after capsid completion. The cleavages products are evicted from the capsid before or during DNA packaging (By similarity). Publication Abstract from PubMed Viruses are responsible for some of the most deadly human diseases, yet available vaccines and antivirals address only a fraction of the potential viral human pathogens. Here, we provide a methodology for managing human herpesvirus (HHV) infection by covalently inactivating the HHV maturational protease via a conserved, non-catalytic cysteine (C161). Using human cytomegalovirus protease (HCMV Pr) as a model, we screened a library of disulfides to identify molecules that tether to C161 and inhibit proteolysis, then elaborated hits into irreversible HCMV Pr inhibitors that exhibit broad-spectrum inhibition of other HHV Pr homologs. We further developed an optimized tool compound targeted toward HCMV Pr and used an integrative structural biology and biochemical approach to demonstrate inhibitor stabilization of HCMV Pr homodimerization, exploiting a conformational equilibrium to block proteolysis. Irreversible HCMV Pr inhibition disrupts HCMV infectivity in cells, providing proof of principle for targeting proteolysis via a non-catalytic cysteine to manage viral infection. Inhibiting a dynamic viral protease by targeting a non-catalytic cysteine.,Hulce KR, Jaishankar P, Lee GM, Bohn MF, Connelly EJ, Wucherer K, Ongpipattanakul C, Volk RF, Chuo SW, Arkin MR, Renslo AR, Craik CS Cell Chem Biol. 2022 Mar 30. pii: S2451-9456(22)00124-6. doi:, 10.1016/j.chembiol.2022.03.007. PMID:35364007 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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