8P42
Full length structure of TcMIP with bound inhibitor NJS227.
Summary for 8P42
| Entry DOI | 10.2210/pdb8p42/pdb |
| Descriptor | Macrophage infectivity potentiator, (2~{S})-1-[(4-fluorophenyl)methylsulfonyl]-~{N}-[(2~{S})-3-(4-fluorophenyl)-1-oxidanylidene-1-(pyridin-3-ylmethylamino)propan-2-yl]piperidine-2-carboxamide, DI(HYDROXYETHYL)ETHER, ... (4 entities in total) |
| Functional Keywords | macrophage, potentiator, soluble, protein, structural protein |
| Biological source | Trypanosoma cruzi |
| Total number of polymer chains | 2 |
| Total formula weight | 37910.83 |
| Authors | Whittaker, J.J.,Guskov, A.,Goretzki, B.,Hellmich, U.A. (deposition date: 2023-05-19, release date: 2024-06-12, Last modification date: 2025-03-26) |
| Primary citation | Perez Carrillo, V.H.,Whittaker, J.J.,Wiedemann, C.,Harder, J.M.,Lohr, T.,Jamithireddy, A.K.,Dajka, M.,Goretzki, B.,Joseph, B.,Guskov, A.,Harmer, N.J.,Holzgrabe, U.,Hellmich, U.A. Structure and Dynamics of Macrophage Infectivity Potentiator Proteins from Pathogenic Bacteria and Protozoans Bound to Fluorinated Pipecolic Acid Inhibitors. J.Med.Chem., 68:5926-5941, 2025 Cited by PubMed Abstract: Macrophage infectivity potentiator (MIP) proteins, found in pro- and eukaryotic pathogens, influence microbial virulence, host cell infection, pathogen replication, and dissemination. MIPs share an FKBP (FK506 binding protein)-like prolyl--isomerase domain, making them attractive targets for inhibitor development. We determined high-resolution crystal structures of and MIPs in complex with fluorinated pipecolic acid inhibitors. The inhibitor binding profiles in solution were compared across , , and MIPs using H, N, and F NMR spectroscopy. Demonstrating the versatility of fluorinated ligands for characterizing inhibitor complexes, F NMR spectroscopy identified differences in ligand binding dynamics across MIPs. EPR spectroscopy and SAXS further revealed inhibitor-induced global structural changes in homodimeric MIP. This study demonstrates the importance of integrating diverse methods to probe protein dynamics and provides a foundation for optimizing MIP-targeted inhibitors in this structurally conserved yet dynamically variable protein family. PubMed: 39976355DOI: 10.1021/acs.jmedchem.5c00134 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.64 Å) |
Structure validation
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