9P0JSummary for 9P0J
| Entry DOI | 10.2210/pdb9p0j/pdb |
| EMDB information | 71076 |
| Descriptor | ATP-dependent 6-phosphofructokinase, liver type, 5-[bis(oxidanylidene)-$l^{5}-sulfanyl]-1,3-benzodioxole, 1,6-di-O-phosphono-beta-D-fructofuranose, ... (6 entities in total) |
| Functional Keywords | phosphofructokinase-1, liver, pfkl, activator, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 82277.21 |
| Authors | Lynch, E.M.,Jiang, X.,Hsu, K.-L.,Kollman, J.M. (deposition date: 2025-06-06, release date: 2026-09-23) |
| Primary citation | Jiang, X.,Lynch, E.M.,Lyu, C.,Wilson, C.N.,Salay, L.E.,Hess, H.T.,Lyons, S.N.,Lu, M.J.,Luo, S.,Kim, G.,Chan, H.R.,Wolfe, W.J.,Zacharias, L.G.,Mathews, T.P.,Lin, Y.C.,Webb, B.A.,Kollman, J.M.,Cambronne, X.A.,Hsu, K.L. A covalent PFKL activator suppresses tumor growth. Nat.Chem.Biol., 2026 Cited by PubMed Abstract: Glycolysis fuels vital cellular functions, and its dysregulation has been implicated in cancer, neurodegeneration, antibiotic resistance and diabetes. The glycolytic dependency of cancer, known as the Warburg effect, represents a key vulnerability for development of targeted anticancer agents; however, the development of such agents remains challenging owing to metabolic heterogeneity and resistance. Here we developed a covalent phosphofructokinase-1 liver type (PFKL) activator that couples glycolytic activation with delivery of a cytotoxic carnitine palmitoyltransferase 2 (CPT2)-targeting payload to cancer cells in vitro and in vivo. The electrophile-drug conjugate site-specifically and proteome-wide selectively modifies K677 in the allosteric effector site to stabilize the R-state tetramer of PFKL, while concomitantly releasing a CPT2-selective inhibitor to destabilize cell metabolism. The delivery mechanism of electrophile-drug conjugates is analogous to that of antibody-drug conjugates, but differentiated by their selective covalent targeting of intracellular proteins. PubMed: 42557312DOI: 10.1038/s41589-026-02289-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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