7A1L
FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH ZN(II) AND 3-methyl-2-oxoglutarate
Summary for 7A1L
| Entry DOI | 10.2210/pdb7a1l/pdb |
| Descriptor | Hypoxia-inducible factor 1-alpha inhibitor, (3~{S})-3-methyl-2-oxidanylidene-pentanedioic acid, ZINC ION, ... (5 entities in total) |
| Functional Keywords | hypoxia-inducible factor asparagine hydroxylase, dioxygenase, oxidoreductase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 40938.07 |
| Authors | Nakashima, Y.,Brewitz, L.,Schofield, C.J. (deposition date: 2020-08-13, release date: 2021-08-25, Last modification date: 2024-01-31) |
| Primary citation | Nakashima, Y.,Brewitz, L.,Tumber, A.,Salah, E.,Schofield, C.J. 2-Oxoglutarate derivatives can selectively enhance or inhibit the activity of human oxygenases. Nat Commun, 12:6478-6478, 2021 Cited by PubMed Abstract: 2-Oxoglutarate (2OG) oxygenases are validated agrochemical and human drug targets. The potential for modulating their activity with 2OG derivatives has not been explored, possibly due to concerns regarding selectivity. We report proof-of-principle studies demonstrating selective enhancement or inhibition of 2OG oxygenase activity by 2-oxo acids. The human 2OG oxygenases studied, factor inhibiting hypoxia-inducible transcription factor HIF-α (FIH) and aspartate/asparagine-β-hydroxylase (AspH), catalyze C3 hydroxylations of Asp/Asn-residues. Of 35 tested 2OG derivatives, 10 enhance and 17 inhibit FIH activity. Comparison with results for AspH reveals that 2OG derivatives selectively enhance or inhibit FIH or AspH. Comparison of FIH structures complexed with 2OG derivatives to those for AspH provides insight into the basis of the observed selectivity. 2-Oxo acid derivatives have potential as drugs, for use in biomimetic catalysis, and in functional studies. The results suggest that the in vivo activity of 2OG oxygenases may be regulated by natural 2-oxo acids other than 2OG. PubMed: 34759269DOI: 10.1038/s41467-021-26673-2 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.29 Å) |
Structure validation
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