6f0w

prolyl hydroxylase in complex with hypoxia inducible factor oxygen degradation domain peptide fragment from Trichoplax adhaerens

spinqualitylabelsall models 6f0w, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6f0w is a 2 chain structure with sequence from Trichoplax adhaerens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.301Å Ligands: CSO, MN, OGA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function I6QVT6_TRIAD Publication Abstract from PubMed Background: In humans and other animals, the chronic hypoxic response is mediated by hypoxia inducible transcription factors (HIFs) which regulate the expression of genes that counteract the effects of limiting oxygen. Prolyl hydroxylases (PHDs) act as hypoxia sensors for the HIF system in organisms ranging from humans to the simplest animal Trichoplax adhaerens. Methods: We report structural and biochemical studies on the T. adhaerens HIF prolyl hydroxylase (TaPHD) that inform about the evolution of hypoxia sensing in animals. Results: High resolution crystal structures (</=1.3 A) of TaPHD, with and without its HIFalpha substrate, reveal remarkable conservation of key active site elements between T. adhaerens and human PHDs, which also manifest in kinetic comparisons. Conclusion: Conserved structural features of TaPHD and human PHDs include those apparently enabling the slow binding/reaction of oxygen with the active site Fe(II), the formation of a stable 2-oxoglutarate complex, and a stereoelectronically promoted change in conformation of the hydroxylated proline-residue. Comparison of substrate selectivity between the human PHDs and TaPHD provides insights into the selectivity determinants of HIF binding by the PHDs, and into the evolution of the multiple HIFs and PHDs present in higher animals. Born to sense: biophysical analyses of the oxygen sensing prolyl hydroxylase from the simplest animal Trichoplax adhaerens.,Lippl K, Boleininger A, McDonough MA, Abboud MI, Tarhonskaya H, Chowdhury R, Loenarz C, Schofield CJ Hypoxia (Auckl). 2018 Nov 9;6:57-71. doi: 10.2147/HP.S174655. eCollection 2018. PMID:30519597 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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