Prolyl hydroxylase domain: Difference between revisions
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[[5l9v]], [[5la9]], [[5las]] - hPHD2 (mutant) + Mn + HIF NODD domain + 2OG<br /> | [[5l9v]], [[5la9]], [[5las]] - hPHD2 (mutant) + Mn + HIF NODD domain + 2OG<br /> | ||
[[3hqu]] - hPHD2 + Fe + HIF 1 α C terminal + quinolin derivative<br /> | [[3hqu]] - hPHD2 + Fe + HIF 1 α C terminal + quinolin derivative<br /> | ||
[[2hbt]], [[2hbu]], [[2g19]], [[2g1m]], [[2y34], [[4bqi | [[2hbt]], [[2hbu]], [[2g19]], [[2g1m]], [[2y34]], [[4bqi]] - hPHD2 + Fe + quinolin derivative<br /> | ||
[[4bqw]], [[4bqx]], [[4bqy]] - hPHD2 + Mn + quinolin derivative<br /> | [[4bqw]], [[4bqx]], [[4bqy]] - hPHD2 + Mn + quinolin derivative<br /> | ||
[[5lat]], [[5lb6]], [[5lbb]], [[5lbc]], [[5lbe]], [[5lbf]], [[4uwd]] - hPHD2 (mutant) + Mn + quinolin derivative<br /> | [[5lat]], [[5lb6]], [[5lbb]], [[5lbc]], [[5lbe]], [[5lbf]], [[4uwd]] - hPHD2 (mutant) + Mn + quinolin derivative<br /> | ||
Revision as of 11:09, 7 October 2020
See also Hydroxylase Prolyl hydroxylase domain (PHD) proteins mediate oxygen-dependent degradation of Hypoxia-inducible factor (HIF) α subunit. They include PHD1, PHD2 and PHD3. The PHD is a Fe+2/oxogluterate (2OG)-dependent enzyme. 3ouh is the crystallized structure of the enzyme PHD2, an oxidoreductase that is 237 amino acids long with a molecular weight of 27 kDa. 3ouh is found in Homo sapiens and is a homolog of EGLN1 found in C. elegans. The protein has three ligands: (a 1-(5-chloro-6-fluoro-1H-benzimidazol-2-yl)-1H-pyrazole-4-carboxylic acid), , and SO4 (a sulfate ion). Water molecules are shown as red spheres. It is involved in mediating physiological responses to hypoxia by degrading the transcription factor of a hypoxia-inducible factor HIF1-α. In hypoxic conditions, the activity of PHD2 lessens, causing an increase in HIF1-α, resulting in secretion of erythropoietin, anaerobic glycolysis, and angiogenesis[1]. [2] For more detalis see Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme.
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3D Structures of prolyl hydroxylase domain3D Structures of prolyl hydroxylase domain
2y33 – hPHD2 + Zn + quinolin derivative – human
3ouh, 3oui, 5v18 - hPHD2 + Fe + inhibitor
4kbz - hPHD2 (mutant) + Fe + inhibitor
5a3u - hPHD2 + Mn + inhibitor
4jzr - hPHD2 + Ni + inhibitor
3ouj - hPHD2 + Fe + 2OG
5l9r - hPHD2 (mutant) + Mn + 2OG
3hqr, 5l9b - hPHD2 (mutant) + Mn + HIF 1 α C terminal + 2OG
5l9v, 5la9, 5las - hPHD2 (mutant) + Mn + HIF NODD domain + 2OG
3hqu - hPHD2 + Fe + HIF 1 α C terminal + quinolin derivative
2hbt, 2hbu, 2g19, 2g1m, 2y34, 4bqi - hPHD2 + Fe + quinolin derivative
4bqw, 4bqx, 4bqy - hPHD2 + Mn + quinolin derivative
5lat, 5lb6, 5lbb, 5lbc, 5lbe, 5lbf, 4uwd - hPHD2 (mutant) + Mn + quinolin derivative
4h6j – hPHD Pasb domain (mutant) + aryl hydrocarbon nuclear translocator (mutant)
5v1b - hPHD1 + Fe + inhibitor
ReferencesReferences
- ↑ Stolze IP, Mole DR, Ratcliffe PJ. Regulation of HIF: prolyl hydroxylases. Novartis Found Symp. 2006;272:15-25; discussion 25-36. PMID:16686427
- ↑ Rosen M D, Venkatesan H, Peltier H M, Bembenek S D, Kanelakis K C, Zhao L X, Leonard B E, Hocutt F M, Wu X, Palomino H L, Brondtetter T I, Haugh P V, Cagnon L, Yan W, Liotta L A, Young A, Mirzadegan T, Shankley N P, Barrett T D, Rabinowitz M H. Benzimidazole-2-pyrazole HIF Prolyl 4-Hydroxylase Inhibitors as Oral Erythropoietin Secretagogues. ACS Medicinal Chemical Letters. 2010 Oct 5.
Created with the participation of Andrew Winslow.