Prolyl hydroxylase domain: Difference between revisions
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[[2hbt]], [[2hbu]] - hPHD2 catalytic domain + Fe + chloro-iodoisoquinolin-carbonyl glycine<br /> | [[2hbt]], [[2hbu]] - hPHD2 catalytic domain + Fe + chloro-iodoisoquinolin-carbonyl glycine<br /> | ||
[[2g19]], [[2g1m]] - hPHD2 catalytic domain + Fe + hydroxy-iodoisoquinolin-carbonyl glycine<br /> | [[2g19]], [[2g1m]] - hPHD2 catalytic domain + Fe + hydroxy-iodoisoquinolin-carbonyl glycine<br /> | ||
[[4h6j]] – hPHD Pasb domain (mutant) + aryl hydrocarbon nuclear translocator (mutant)<br /> | |||
==References== | ==References== | ||
Revision as of 13:36, 27 March 2016
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: O14 (a 1-(5-chloro-6-fluoro-1H-benzimidazol-2-yl)-1H-pyrazole-4-carboxylic acid), FE2 (an iron ion), and SO4 (a sulfate ion). It is involved in mediating physiological responses to hypoxia by degrading the transcription factor of a hypoxia-inducible factor HIF1-alpha. In hypoxic conditions, the activity of PHD2 lessens, causing an increase in HIF1-alpha, resulting in secretion of erythropoietin, anaerobic glycolysis, and angiogenesis. [1] For more detalis see Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme.
3D Structures of prolyl hydroxylase domain3D Structures of prolyl hydroxylase domain
2y33 – hPHD2 catalytic domain + Zn + chloro-iodoisoquinolin-carbonyl glycine – human
2y34 - hPHD2 catalytic domain + Fe + chloro-iodoisoquinolin-carbonyl glycine
3ouh, 3oui - hPHD2 catalytic domain + Fe + inhibitor
3ouj - hPHD2 catalytic domain + Fe + 2OG
3hqr - hPHD2 catalytic domain (mutant) + Mn + HIF 1 α C terminal + oxalylglycine
3hqu - hPHD2 catalytic domain + Fe + HIF 1 α C terminal + chloro-iodoisoquinolin-carbonyl glycine
2hbt, 2hbu - hPHD2 catalytic domain + Fe + chloro-iodoisoquinolin-carbonyl glycine
2g19, 2g1m - hPHD2 catalytic domain + Fe + hydroxy-iodoisoquinolin-carbonyl glycine
4h6j – hPHD Pasb domain (mutant) + aryl hydrocarbon nuclear translocator (mutant)
ReferencesReferences
- ↑ 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.