6CBH
Macrophage Migration Inhibitory Factor in Complex with a Pyrazole Inhibitor (8m)
Summary for 6CBH
| Entry DOI | 10.2210/pdb6cbh/pdb |
| Descriptor | Macrophage migration inhibitory factor, SULFATE ION, ISOPROPYL ALCOHOL, ... (6 entities in total) |
| Functional Keywords | inhibitor, complex, cytokine |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 3 |
| Total formula weight | 38294.25 |
| Authors | Robertson, M.J.,Krimmer, S.G.,Jorgensen, W.L. (deposition date: 2018-02-02, release date: 2018-04-04, Last modification date: 2024-03-13) |
| Primary citation | Trivedi-Parmar, V.,Robertson, M.J.,Cisneros, J.A.,Krimmer, S.G.,Jorgensen, W.L. Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor. ChemMedChem, 13:1092-1097, 2018 Cited by PubMed Abstract: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is implicated in the regulation of inflammation, cell proliferation, and neurological disorders. MIF is also an enzyme that functions as a keto-enol tautomerase. Most potent MIF tautomerase inhibitors incorporate a phenol, which hydrogen bonds to Asn97 in the active site. Starting from a 113-μm docking hit, we report results of structure-based and computer-aided design that have provided substituted pyrazoles as phenol alternatives with potencies of 60-70 nm. Crystal structures of complexes of MIF with the pyrazoles highlight the contributions of hydrogen bonding with Lys32 and Asn97, and aryl-aryl interactions with Tyr36, Tyr95, and Phe113 to the binding. PubMed: 29575754DOI: 10.1002/cmdc.201800158 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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