8P3C

Full length structure of BpMIP with bound inhibitor NJS227.

8P3C の概要

• エントリーDOI: 10.2210/pdb8p3c/pdb
• 分子名称: Peptidyl-prolyl cis-trans isomerase, (2~{S})-1-[(4-fluorophenyl)methylsulfonyl]-~{N}-[(2~{S})-3-(4-fluorophenyl)-1-oxidanylidene-1-(pyridin-3-ylmethylamino)propan-2-yl]piperidine-2-carboxamide, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: macrophage, potentiator, soluble, protein, structural protein
• 由来する生物種: Burkholderia pseudomallei
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14469.12

構造登録者

Whittaker, J.J.,Guskov, A.,Goretzki, B.,Hellmich, U.A. (登録日: 2023-05-17, 公開日: 2024-06-12, 最終更新日: 2025-03-26)

主引用文献

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

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: 39976355
DOI: 10.1021/acs.jmedchem.5c00134

実験手法

X-RAY DIFFRACTION (2.02 Å)