View source for 4j25


==Crystal structure of a Pseudomonas putida prolyl-4-hydroxylase (P4H)==
<StructureSection load='4j25' size='340' side='right'caption='[[4j25]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4j25]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_putida_KT2440 Pseudomonas putida KT2440]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J25 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J25 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]] 1.97&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=4j25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j25 OCA], [https://pdbe.org/4j25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j25 RCSB], [https://www.ebi.ac.uk/pdbsum/4j25 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j25 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q88CM1_PSEPK Q88CM1_PSEPK] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The roles of 2-oxoglutarate (2OG)-dependent prolyl-hydroxylases in eukaryotes include collagen stabilization, hypoxia sensing, and translational regulation. The hypoxia-inducible factor (HIF) sensing system is conserved in animals, but not in other organisms. However, bioinformatics imply that 2OG-dependent prolyl-hydroxylases (PHDs) homologous to those acting as sensing components for the HIF system in animals occur in prokaryotes. We report cellular, biochemical, and crystallographic analyses revealing that Pseudomonas prolyl-hydroxylase domain containing protein (PPHD) contain a 2OG oxygenase related in structure and function to the animal PHDs. A Pseudomonas aeruginosa PPHD knockout mutant displays impaired growth in the presence of iron chelators and increased production of the virulence factor pyocyanin. We identify elongation factor Tu (EF-Tu) as a PPHD substrate, which undergoes prolyl-4-hydroxylation on its switch I loop. A crystal structure of PPHD reveals striking similarity to human PHD2 and a Chlamydomonas reinhardtii prolyl-4-hydroxylase. A crystal structure of PPHD complexed with intact EF-Tu reveals that major conformational changes occur in both PPHD and EF-Tu, including a &gt;20-A movement of the EF-Tu switch I loop. Comparison of the PPHD structures with those of HIF and collagen PHDs reveals conservation in substrate recognition despite diverse biological roles and origins. The observed changes will be useful in designing new types of 2OG oxygenase inhibitors based on various conformational states, rather than active site iron chelators, which make up most reported 2OG oxygenase inhibitors. Structurally informed phylogenetic analyses suggest that the role of prolyl-hydroxylation in human hypoxia sensing has ancient origins.

Human oxygen sensing may have origins in prokaryotic elongation factor Tu prolyl-hydroxylation.,Scotti JS, Leung IK, Ge W, Bentley MA, Paps J, Kramer HB, Lee J, Aik W, Choi H, Paulsen SM, Bowman LA, Loik ND, Horita S, Ho CH, Kershaw NJ, Tang CM, Claridge TD, Preston GM, McDonough MA, Schofield CJ Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):13331-6. doi:, 10.1073/pnas.1409916111. Epub 2014 Sep 2. PMID:25197067<ref>PMID:25197067</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4j25" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas putida KT2440]]
[[Category: McDonough MA]]
[[Category: Schofield CJ]]
[[Category: Scotti JS]]