Prolyl hydroxylase domain: Difference between revisions
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'''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 [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and is a homolog of [http://en.wikipedia.org/wiki/EGLN1 EGLN1] found in [http://en.wikipedia.org/wiki/Caenorhabditis_elegans C. elegans]. | '''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 [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and is a homolog of [http://en.wikipedia.org/wiki/EGLN1 EGLN1] found in [http://en.wikipedia.org/wiki/Caenorhabditis_elegans 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 [http://en.wikipedia.org/wiki/Hypoxia_(medical) 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. | 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 [http://en.wikipedia.org/wiki/Hypoxia_(medical) 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<ref>PMID:16686427</ref>. | ||
<ref>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.</ref> For more detalis see [[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]. | <ref>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.</ref> For more detalis see [[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]. | ||
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[[4h6j]] – hPHD Pasb domain (mutant) + aryl hydrocarbon nuclear translocator (mutant)<br /> | [[4h6j]] – hPHD Pasb domain (mutant) + aryl hydrocarbon nuclear translocator (mutant)<br /> | ||
==References== | ==References== | ||
<references/> | <references/> | ||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||
<br /> | <br /> | ||
Created with the participation of [[User:Andrew Winslow|Andrew Winslow]]. | Created with the participation of [[User:Andrew Winslow|Andrew Winslow]]. | ||
Revision as of 13:41, 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]. [2] 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
- ↑ 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.