6t8m: Difference between revisions
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The | ==Prolyl Hydroxylase (PHD) involved in hypoxia sensing by Dictyostelium discoideum== | ||
<StructureSection load='6t8m' size='340' side='right'caption='[[6t8m]], [[Resolution|resolution]] 2.02Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6t8m]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Dictyostelium_discoideum Dictyostelium discoideum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T8M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T8M FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.02Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6t8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t8m OCA], [https://pdbe.org/6t8m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t8m RCSB], [https://www.ebi.ac.uk/pdbsum/6t8m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t8m ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/P4HA_DICDI P4HA_DICDI] Catalyzes the post-translational formation of 4-hydroxyproline. Probably hydroxylates skp1 on Pro-143.<ref>PMID:11358877</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In animals, the response to chronic hypoxia is mediated by prolyl-hydroxylases (PHDs) that regulate the levels of hypoxia inducible transcription factor a (HIFalpha). PHD homologues exist in other types of eukaryotes and prokaryotes where they act on non-HIF substrates. To gain insight into the factors underlying different PHD substrates and properties, we carried out biochemical and biophysical studies on PHD homologues from the slime mold, Dictyostelium discoideum, and the protozoan parasite, Toxoplasma gondii, both lacking HIF. The respective prolyl-hydroxylases (DdPhyA and TgPhyA) catalyze prolyl-hydroxylation of S-Phase Kinase Associated Protein 1 (Skp1), a reaction enabling adaptation to different dioxygen availability. Assays with full length Skp1 substrates reveal substantial differences in the kinetic properties of DdPhyA and TgPhyA, both with respect to each other and compared with human PHD2; consistent with cellular studies TgPhyA is more active at low dioxygen concentrations than DdPhyA. TgSkp1 is a DdPhyA substrate and DdSkp1 is a TgPhyA substrate. No cross-reactivity was detected between DdPhyA/TgPhyA substrates and human PHD2. The human Skp1 E147P variant is a DdPhyA and TgPhyA substrate, suggesting some retention of ancestral interactions. Crystallographic analysis of DdPhyA enables comparisons with homologues from humans, Trichoplax adhaerens, and prokaryotes, TgPhyA informing on differences in mobile elements involved in substrate binding and catalysis. In DdPhyA, two mobile loops that enclose substrates in the PHDs are conserved, but the C-terminal helix of the PHDs is strikingly absent. The combined results support the proposal that PHD homologues have evolved kinetic and structural features suited to their specific sensing roles. | |||
Biochemical and biophysical analyses of hypoxia sensing prolyl hydroxylases from Dictyostelium discoideum and Toxoplasma gondii.,Liu T, Abboud MI, Chowdhury R, Tumber A, Hardy AP, Lippl K, Lohans CT, Pires E, Wickens J, McDonough MA, West CM, Schofield CJ J Biol Chem. 2020 Sep 15. pii: RA120.013998. doi: 10.1074/jbc.RA120.013998. PMID:32934009<ref>PMID:32934009</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6t8m" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Dictyostelium discoideum]] | |||
[[Category: Large Structures]] | |||
[[Category: Chowdhury R]] | |||
[[Category: Clifton IJ]] | |||
[[Category: Liu T]] | |||
[[Category: McDonough MA]] | |||
[[Category: Schofield CJ]] | |||