5A3U
HIF prolyl hydroxylase 2 (PHD2/EGLN1) in complex with 6-(5-oxo-4-(1H- 1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl)nicotinic acid
Summary for 5A3U
| Entry DOI | 10.2210/pdb5a3u/pdb |
| Related | 2G19 2G1M 4BQW 4BQX 4BQY |
| Descriptor | EGL NINE HOMOLOG 1, MANGANESE (II) ION, 6-(5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl)nicotinic acid (3 entities in total) |
| Functional Keywords | oxidoreductase, non-heme, iron, 2-oxoglutarate, dioxygenase, hypoxia-inducible factor, hif, hif prolyl hydroxylase domain 2, phd2, egln, oxygenase, hypoxia, dna-binding, metal-binding, transcription, helix-loop-helix-beta, dsbh, facial triad, asparaginyl/ aspartyl hydroxylase, transcription and epigenetic regulation, signaling, development, cell structure, ankyrin repeat domain, ard, beta-hydroxylation, transcription activator/inhibitor, phosphorylation, s-nitrosylation |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 3 |
| Total formula weight | 85272.30 |
| Authors | Chowdhury, R.,Gomez-Perez, V.,Schofield, C.J. (deposition date: 2015-06-03, release date: 2015-06-17, Last modification date: 2024-01-10) |
| Primary citation | Chan, M.C.,Atasoylu, O.,Hodson, E.,Tumber, A.,Leung, I.K.H.,Chowdhury, R.,Gomez-Perez, V.,Demetriades, M.,Rydzik, A.M.,Holt-Martyn, J.,Tian, Y.,Bishop, T.,Claridge, T.D.W.,Kawamura, A.,Pugh, C.W.,Ratcliffe, P.J.,Schofield, C.J. Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain. Plos One, 10:32004-, 2015 Cited by PubMed Abstract: As part of the cellular adaptation to limiting oxygen availability in animals, the expression of a large set of genes is activated by the upregulation of the hypoxia-inducible transcription factors (HIFs). Therapeutic activation of the natural human hypoxic response can be achieved by the inhibition of the hypoxia sensors for the HIF system, i.e. the HIF prolyl-hydroxylases (PHDs). Here, we report studies on tricyclic triazole-containing compounds as potent and selective PHD inhibitors which compete with the 2-oxoglutarate co-substrate. One compound (IOX4) induces HIFα in cells and in wildtype mice with marked induction in the brain tissue, revealing that it is useful for studies aimed at validating the upregulation of HIF for treatment of cerebral diseases including stroke. PubMed: 26147748DOI: 10.1371/JOURNAL.PONE.0132004 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.3 Å) |
Structure validation
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