Prolyl hydroxylase domain: Difference between revisions
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{{STRUCTURE_3hqu| PDB=3hqu | SIZE=400| SCENE= |right|CAPTION=PHD2 with Fe+2 complex with HIF 1 α C terminal and iodoisoquinolin inhibitor, [[3hqu]] }} | {{STRUCTURE_3hqu| PDB=3hqu | SIZE=400| SCENE= |right|CAPTION=PHD2 with Fe+2 complex with HIF 1 α C terminal and iodoisoquinolin inhibitor, [[3hqu]] }} | ||
'''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. | '''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. | |||
<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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[[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 /> | ||
==References== | |||
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[[Category:Topic Page]] | [[Category:Topic Page]] | ||
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Created with the participation of [[User:Andrew Winslow|Andrew Winslow]]. | |||