4b65: Difference between revisions

Latest revision as of 11:44, 20 December 2023

A. fumigatus ornithine hydroxylase (SidA), reduced state bound to NADP(H)

Structural highlights

4b65 is a 1 chain structure with sequence from Aspergillus fumigatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.32Å
Ligands:	FAD, GOL, NDP, SO4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

SidA from the human pathogen Aspergillus fumigatus catalyzes the generation of N(5)-hydroxyornithine in the biosynthesis of siderophores, a reaction essential for virulence. The crystal structures of SidA in complex with ornithine and lysine reveal the geometry of the interactions among flavin, NADP(+), and the substrate amine group that underlie the hydroxylation reaction. The structural elucidation of the enzyme in complex with arginine provides insight into the role of electrostatics and hydrogen bonding in the mechanism of oxygen activation in this family of enzymes.

Structural insight into the mechanism of oxygen activation and substrate selectivity of flavin-dependent N-hydroxylating monooxygenases.,Franceschini S, Fedkenheuer M, Vogelaar NJ, Robinson HH, Sobrado P, Mattevi A Biochemistry. 2012 Sep 11;51(36):7043-5. Epub 2012 Aug 30. PMID:22928747^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Schrettl M, Bignell E, Kragl C, Joechl C, Rogers T, Arst HN Jr, Haynes K, Haas H. Siderophore biosynthesis but not reductive iron assimilation is essential for Aspergillus fumigatus virulence. J Exp Med. 2004 Nov 1;200(9):1213-9. Epub 2004 Oct 25. PMID:15504822 doi:https://dx.doi.org/jem.20041242
↑ Hissen AH, Wan AN, Warwas ML, Pinto LJ, Moore MM. The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N5-oxygenase, is required for virulence. Infect Immun. 2005 Sep;73(9):5493-503. PMID:16113265 doi:https://dx.doi.org/10.1128/IAI.73.9.5493-5503.2005
↑ Chocklett SW, Sobrado P. Aspergillus fumigatus SidA is a highly specific ornithine hydroxylase with bound flavin cofactor. Biochemistry. 2010 Aug 10;49(31):6777-83. doi: 10.1021/bi100291n. PMID:20614882 doi:https://dx.doi.org/10.1021/bi100291n
↑ Romero E, Fedkenheuer M, Chocklett SW, Qi J, Oppenheimer M, Sobrado P. Dual role of NADP(H) in the reaction of a flavin dependent N-hydroxylating monooxygenase. Biochim Biophys Acta. 2012 Jun;1824(6):850-7. doi: 10.1016/j.bbapap.2012.03.004. , Epub 2012 Mar 27. PMID:22465572 doi:https://dx.doi.org/10.1016/j.bbapap.2012.03.004
↑ Franceschini S, Fedkenheuer M, Vogelaar NJ, Robinson HH, Sobrado P, Mattevi A. Structural insight into the mechanism of oxygen activation and substrate selectivity of flavin-dependent N-hydroxylating monooxygenases. Biochemistry. 2012 Sep 11;51(36):7043-5. Epub 2012 Aug 30. PMID:22928747 doi:https://dx.doi.org/10.1021/bi301072w

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Schrettl M, Bignell E, Kragl C, Joechl C, Rogers T, Arst HN Jr, Haynes K, Haas H. Siderophore biosynthesis but not reductive iron assimilation is essential for Aspergillus fumigatus virulence. J Exp Med. 2004 Nov 1;200(9):1213-9. Epub 2004 Oct 25. PMID:15504822 doi:https://dx.doi.org/jem.20041242

[2] Hissen AH, Wan AN, Warwas ML, Pinto LJ, Moore MM. The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N5-oxygenase, is required for virulence. Infect Immun. 2005 Sep;73(9):5493-503. PMID:16113265 doi:https://dx.doi.org/10.1128/IAI.73.9.5493-5503.2005

[3] Chocklett SW, Sobrado P. Aspergillus fumigatus SidA is a highly specific ornithine hydroxylase with bound flavin cofactor. Biochemistry. 2010 Aug 10;49(31):6777-83. doi: 10.1021/bi100291n. PMID:20614882 doi:https://dx.doi.org/10.1021/bi100291n

[4] Romero E, Fedkenheuer M, Chocklett SW, Qi J, Oppenheimer M, Sobrado P. Dual role of NADP(H) in the reaction of a flavin dependent N-hydroxylating monooxygenase. Biochim Biophys Acta. 2012 Jun;1824(6):850-7. doi: 10.1016/j.bbapap.2012.03.004. , Epub 2012 Mar 27. PMID:22465572 doi:https://dx.doi.org/10.1016/j.bbapap.2012.03.004

[5] Franceschini S, Fedkenheuer M, Vogelaar NJ, Robinson HH, Sobrado P, Mattevi A. Structural insight into the mechanism of oxygen activation and substrate selectivity of flavin-dependent N-hydroxylating monooxygenases. Biochemistry. 2012 Sep 11;51(36):7043-5. Epub 2012 Aug 30. PMID:22928747 doi:https://dx.doi.org/10.1021/bi301072w

[1]

[2]

[3]

[4]

[5]

@@ Line 3: / Line 3: @@
 <StructureSection load='4b65' size='340' side='right'caption='[[4b65]], [[Resolution|resolution]] 2.32&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4b65]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspfm Aspfm]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B65 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B65 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4b65]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B65 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B65 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.32&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4b63|4b63]], [[4b64|4b64]], [[4b66|4b66]], [[4b67|4b67]], [[4b68|4b68]], [[4b69|4b69]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4b65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b65 OCA], [https://pdbe.org/4b65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b65 RCSB], [https://www.ebi.ac.uk/pdbsum/4b65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b65 ProSAT]</span></td></tr>
 </table>
+== 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;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Aspfm]]
+[[Category: Aspergillus fumigatus]]
 [[Category: Large Structures]]
-[[Category: Fedkenheuer, M]]
+[[Category: Fedkenheuer M]]
-[[Category: Franceschini, S]]
+[[Category: Franceschini S]]
-[[Category: Mattevi, A]]
+[[Category: Mattevi A]]
-[[Category: Robinson, H H]]
+[[Category: Robinson HH]]
-[[Category: Sobrado, P]]
+[[Category: Sobrado P]]
-[[Category: Vogelaar, N J]]
+[[Category: Vogelaar NJ]]
-[[Category: Flavin]]
-[[Category: Oxidoreductase]]
-[[Category: Siderophore]]

4b65: Difference between revisions

Latest revision as of 11:44, 20 December 2023

A. fumigatus ornithine hydroxylase (SidA), reduced state bound to NADP(H)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools