4exh | pdb_00004exh

The crystal structure of xmrv protease complexed with acetyl-pepstatin

spinqualitylabelsall models 4exh, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4exh is a 5 chain structure with sequence from Dg-75 murine leukemia virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FMT NonStd Res: ACE, STA Related: 3sm1 Gene: GAG-POL (DG-75 Murine leukemia virus) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The kinetic properties of two classical inhibitors of aspartic proteases, pepstatin A and acetyl-pepstatin, were compared in their interactions with human immunodeficiency virus type-1 (HIV-1) and xenotropic murine leukemia virus-related virus (XMRV) proteases (PRs). Both compounds are substantially weaker inhibitors of XMRV PR than of HIV-1 PR. Previous kinetic and structural studies characterized HIV-1 PR/acetyl-pepstatin and XMRV PR/pepstain A complexes and suggested dramatically different binding modes. Interaction energies were calculated for the possible binding modes and suggested a strong preference for the one inhibitor-binding mode for HIV-1 PR, and two inhibitor-binding mode for XMRV PR-pepstatin A interaction. Comparison of the molecular models suggested that in the case of XMRV PR, the relatively unfavorable interactions at S3' and the favorable interactions at S4 and S4' sites with the statine residues may shift the ground state binding towards the two inhibitor-binding mode, whereas the single molecule ground state binding of statines to the HIV-1 PR appear to be more favorable. The preferred single molecular binding to HIV-1 PR allows the formation of the transition state complex, represented by substantially better binding constants. Intriguingly, crystal structure of the complex of acetyl-pepstatin with XMRV PR has shown a mixed type of binding: the unusual binding mode of two molecules of the inhibitor to the enzyme, in a mode very similar to the previously determined complex with pepstatin A, together with the classical binding mode found for HIV-1 PR. The structure is thus in good agreement with the very similar interaction energies calculated for the two types of binding. NX43Inhibition of XMRV and HIV-1 proteases by pepstatin A and acetyl-pepstatin.,Matuz K, Motyan J, Li M, Wlodawer A, Tozser J FEBS J. 2012 Jul 17. doi: 10.1111/j.1742-4658.2012.08714.x. PMID:22804908 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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