2pbk

Crystal structure of KSHV protease in complex with hexapeptide phosphonate inhibitor

spinqualitylabelsall models 2pbk, resolution 1.73Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2pbk is a 4 chain structure with sequence from Human gammaherpesvirus 8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.73Å Ligands: ACE, ACT, GG7, TBG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SCAF_HHV8P Acts as a scaffold protein by binding major capsid protein in the cytoplasm, inducing the nuclear localization of both proteins. Multimerizes in the nucleus such as major capsid protein forms the icosahedral T=16 capsid. Autocatalytic cleavage releases the assembly protein, and subsequently abolishes interaction with major capsid protein. Cleavages products are evicted from the capsid before or during DNA packaging.[HAMAP-Rule:MF_04008] Protease that plays an essential role in virion assembly within the nucleus. Catalyzes the cleavage of the assembly protein after formation of the spherical procapsid. By that cleavage, the capsid matures and gains its icosahedral shape. The cleavage sites seem to include -Ala-Ser-, -Ala-Ala-, as well as Ala-Thr bonds. Assemblin and cleavages products are evicted from the capsid before or during DNA packaging.[HAMAP-Rule:MF_04008] Plays a major role in capsid assembly. Acts as a scaffold protein by binding major capsid protein. Multimerizes in the nucleus such as major capsid protein 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.[HAMAP-Rule:MF_04008] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The herpesvirus proteases are an example in which allosteric regulation of an enzyme activity is achieved through the formation of quaternary structure. Here, we report a 1.7 A resolution structure of Kaposi's sarcoma-associated herpesvirus protease in complex with a hexapeptide transition state analogue that stabilizes the dimeric state of the enzyme. Extended substrate binding sites are induced upon peptide binding. In particular, 104 A2 of surface are buried in the newly formed S4 pocket when tyrosine binds at this site. The peptide inhibitor also induces a rearrangement of residues that stabilizes the oxyanion hole and the dimer interface. Concomitant with the structural changes, an increase in catalytic efficiency of the enzyme results upon extended substrate binding. A nearly 20-fold increase in kcat/KM results upon extending the peptide substrate from a tetrapeptide to a hexapeptide exclusively due to a KM effect. This suggests that the mechanism by which herpesvirus proteases achieve their high specificity is by using extended substrates to modulate both the structure and activity of the enzyme. Substrate modulation of enzyme activity in the herpesvirus protease family.,Lazic A, Goetz DH, Nomura AM, Marnett AB, Craik CS J Mol Biol. 2007 Nov 2;373(4):913-23. Epub 2007 Aug 16. PMID:17870089 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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