3h89

A combined crystallographic and molecular dynamics study of cathepsin-L retro-binding inhibitors(compound 4)

spinqualitylabelsall models 3h89, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3h89 is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NSX Related: 3h8b, 3h8c Gene: Catehpsin L (HUMAN) Activity: Cathepsin L, with EC number 3.4.22.15 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CATL1_HUMAN] Important for the overall degradation of proteins in lysosomes. 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 We report the crystal structures of three noncovalent retrobinding inhibitors in complex with mature cathepsin L up to resolutions of 2.5, 1.8, and 2.5 A, respectively. These inhibitors were Bpa-(Nepsilon-Bpa)Lys-DArg-Tyr-Npe, Bpa-(Nepsilon-Bpa)Lys-DArg-Phe-Npe, and Bpa-MCys-DArg-Phe-Npe, where Bpa = biphenylacetyl and Pea = N-phenylethyl. These were selected to clarify the binding mode of the biphenyl groups in the S' subsites because the addition of a second biphenyl does not improve potency. Examination of the symmetry-related monomers in the crystal structures revealed inhibitor-inhibitor crystal packing interactions. Molecular dynamics simulations were then used to explore the structure and dynamical behavior of the isolated protein-ligand complexes in solution. In the simulations, the backbone biphenyl groups for all three inhibitors ended up in the same location despite having started out in different orientations in the initial crystal structure conformations. The lack of improved potency of the larger inhibitors over the smaller one is attributed to a correspondingly greater entropic cost of binding. A combined crystallographic and molecular dynamics study of cathepsin L retrobinding inhibitors.,Shenoy RT, Chowdhury SF, Kumar S, Joseph L, Purisima EO, Sivaraman J J Med Chem. 2009 Oct 22;52(20):6335-46. PMID:19761244 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cathepsin

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