6x0h: Difference between revisions
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<StructureSection load='6x0h' size='340' side='right'caption='[[6x0h]], [[Resolution|resolution]] 2.09Å' scene=''> | <StructureSection load='6x0h' size='340' side='right'caption='[[6x0h]], [[Resolution|resolution]] 2.09Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6x0h]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6x0h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus_Af293 Aspergillus fumigatus Af293]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6X0H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6X0H FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.087Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=6x0h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x0h OCA], [https://pdbe.org/6x0h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x0h RCSB], [https://www.ebi.ac.uk/pdbsum/6x0h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x0h ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/SIDA_ASPFU SIDA_ASPFU] Catalyzes the conversion of L-ornithine to N(5)-hydroxyornithine, the first step in the biosynthesis of all hydroxamate-containing siderophores, such as the secreted triacetylfusarinine C (TAFC) involved in iron uptake and the intracellular iron storage compound desferriferricrocin (DFFC). Highly specific for its substrate, only hydrolyzing l-ornithine. Has preference for NADPH over NADH, NADPH playing a role in stabilization of the C4a-hydroperoxyflavin intermediate. Essential for virulence.<ref>PMID:15504822</ref> <ref>PMID:16113265</ref> <ref>PMID:20614882</ref> <ref>PMID:22465572</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Aspergillus fumigatus Af293]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Campbell | [[Category: Campbell AC]] | ||
[[Category: Tanner | [[Category: Tanner JJ]] | ||
Latest revision as of 17:40, 18 October 2023
Structure of oxidized SidA ornithine hydroxylase with the FAD in the "out" conformationStructure of oxidized SidA ornithine hydroxylase with the FAD in the "out" conformation
Structural highlights
FunctionSIDA_ASPFU Catalyzes the conversion of L-ornithine to N(5)-hydroxyornithine, the first step in the biosynthesis of all hydroxamate-containing siderophores, such as the secreted triacetylfusarinine C (TAFC) involved in iron uptake and the intracellular iron storage compound desferriferricrocin (DFFC). Highly specific for its substrate, only hydrolyzing l-ornithine. Has preference for NADPH over NADH, NADPH playing a role in stabilization of the C4a-hydroperoxyflavin intermediate. Essential for virulence.[1] [2] [3] [4] Publication Abstract from PubMedThe SidA ornithine hydroxylase from Aspergillus fumigatus is a fungal disease drug target involved in the production of hydroxamate containing siderophores, which are used by the pathogen to sequester iron. SidA is an N-monooxygenase that catalyzes the NADPH-dependent hydroxylation of L-ornithine through a multistep oxidative mechanism, utilizing a C4a-hydroperoxyflavin intermediate. Here we present four new crystal structures of SidA in various redox- and ligation states, including the first structure of oxidized SidA without NADP(H) or L-ornithine bound (resting state). The resting state structure reveals a new "out" active site conformation characterized by large rotations of the FAD isoalloxazine around the C1'-C2' and N10-C1' bonds, coupled to a 10 A movement of the Tyr-loop. Additional structures show that either flavin reduction or the binding of NADP(H) is sufficient to drive the FAD to the "in" conformation. The structures also reveal protein conformational changes associated with the binding of NADP(H) and L-ornithine. Some of these residues were probed using site-directed mutagenesis. Docking was used to explore the active site of the "out" conformation. These calculations identified two potential ligand-binding sites. Altogether, our results provide new information about conformational dynamics in flavin-dependent monooxygenases. Understanding the different active site conformations that appear during the catalytic cycle may allow fine tuning of inhibitor discovery efforts. Trapping conformational states of a flavin-dependent N-monooxygenase in crystallo reveals protein and flavin dynamics.,Campbell AC, Stiers KM, Martin Del Campo JS, Mehra-Chaudhary R, Sobrado P, Tanner JJ J Biol Chem. 2020 Jul 28. pii: RA120.014750. doi: 10.1074/jbc.RA120.014750. PMID:32723870[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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