1bf7

Theoretical Model: The protein structure described on this page was determined theoretically, and hence should be interpreted with caution.

MOLECULAR MODEL OF THE CATHEPSIN B-LIKE CYSTEINE PROTEASE FROM THE PROTOZOAN PARASITE LEISHMANIA MAJOR, THEORETICAL MODEL

spinqualitylabelsall models 1bf7 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, PDBsum, ProSAT Publication Abstract from PubMed The crystal structures of papain, cruzain, and human liver cathepsin B were used to build homology-based enzyme models of a cathepsin L-like cysteine protease (cpL) and a cathepsin B-like cysteine protease (cpB) from the protozoan parasite Leishmania major. Although structurally a member of the cathepsin B subfamily, the L. major cpB is not able to cleave synthetic substrates having an arginine in position P2. This biochemical property correlates with the prediction of a glycine instead of a glutamic acid at position 205 (papain numbering). The modeled active sites of the L. major cpB and cpL were used to screen the Available Chemicals Directory (a database of about 150,000 commercially available compounds) for potential cysteine protease inhibitors, using DOCK3.5. Based on both steric and force field considerations, 69 compounds were selected. Of these, 18 showed IC50's between 50 and 100 microM and 3 had IC50's below 50 microM. A secondary library of compounds, originally derived from a structural screen against the homologous protease of Plasmodium falciparum (falcipain), and subsequently expanded by combinatorial chemistry, was also screened. Three inhibitors were identified which were not only effective against the L. major protease but also inhibited parasite growth at 5-50 microM. Leishmania major: molecular modeling of cysteine proteases and prediction of new nonpeptide inhibitors.,Selzer PM, Chen X, Chan VJ, Cheng M, Kenyon GL, Kuntz ID, Sakanari JA, Cohen FE, McKerrow JH Exp Parasitol. 1997 Nov;87(3):212-21. PMID:9371086 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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