2PBK
Crystal structure of KSHV protease in complex with hexapeptide phosphonate inhibitor
Summary for 2PBK
| Entry DOI | 10.2210/pdb2pbk/pdb |
| Related | 1FL1 |
| Related PRD ID | PRD_000347 |
| Descriptor | KSHV protease, hexapeptide phosphonate inhibitor, ACETATE ION, ... (4 entities in total) |
| Functional Keywords | kshv, kshv protease, herpesvirus protease, viral protease, viral protein, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Human herpesvirus More |
| Total number of polymer chains | 4 |
| Total formula weight | 51736.07 |
| Authors | Lazic, A.,Goetz, D.H. (deposition date: 2007-03-28, release date: 2007-12-25, Last modification date: 2024-10-16) |
| Primary citation | Lazic, A.,Goetz, D.H.,Nomura, A.M.,Marnett, A.B.,Craik, C.S. Substrate modulation of enzyme activity in the herpesvirus protease family. J.Mol.Biol., 373:913-923, 2007 Cited by PubMed Abstract: 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. PubMed: 17870089DOI: 10.1016/j.jmb.2007.07.073 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.73 Å) |
Structure validation
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