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| | ==Crystal structure of IsdI in complex with Cobalt protoporphyrin IX== | | ==Crystal structure of IsdI in complex with Cobalt protoporphyrin IX== |
| - | <StructureSection load='2zdp' size='340' side='right' caption='[[2zdp]], [[Resolution|resolution]] 1.50Å' scene=''> | + | <StructureSection load='2zdp' size='340' side='right'caption='[[2zdp]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2zdp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZDP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZDP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2zdp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZDP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=COH:PROTOPORPHYRIN+IX+CONTAINING+CO'>COH</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]] 1.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zdo|2zdo]], [[1xbw|1xbw]], [[1sqe|1sqe]]</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=COH:PROTOPORPHYRIN+IX+CONTAINING+CO'>COH</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">isdI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</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=2zdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zdp OCA], [https://pdbe.org/2zdp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zdp RCSB], [https://www.ebi.ac.uk/pdbsum/2zdp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zdp ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2zdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zdp OCA], [http://pdbe.org/2zdp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zdp RCSB], [http://www.ebi.ac.uk/pdbsum/2zdp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zdp ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HDOX2_STAAN HDOX2_STAAN]] Allows bacterial pathogens to use the host heme as an iron source. Catalyzes the oxidative degradation of the heme macrocyclic porphyrin ring to the oxo-bilirubin chromophore staphylobilin (a mixture of the linear tetrapyrroles 5-oxo-delta-bilirubin and 15-oxo-beta-bilirubin) in the presence of a suitable electron donor such as ascorbate or NADPH--cytochrome P450 reductase, with subsequent release of free iron.[HAMAP-Rule:MF_01272]<ref>PMID:18713745</ref> <ref>PMID:20180905</ref> | + | [https://www.uniprot.org/uniprot/HDOX2_STAAN HDOX2_STAAN] Allows bacterial pathogens to use the host heme as an iron source. Catalyzes the oxidative degradation of the heme macrocyclic porphyrin ring to the oxo-bilirubin chromophore staphylobilin (a mixture of the linear tetrapyrroles 5-oxo-delta-bilirubin and 15-oxo-beta-bilirubin) in the presence of a suitable electron donor such as ascorbate or NADPH--cytochrome P450 reductase, with subsequent release of free iron.[HAMAP-Rule:MF_01272]<ref>PMID:18713745</ref> <ref>PMID:20180905</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Heme oxygenase|Heme oxygenase]] | + | *[[Heme oxygenase 3D structures|Heme oxygenase 3D structures]] |
| - | *[[Monooxygenase|Monooxygenase]] | + | *[[Monooxygenase 3D structures|Monooxygenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Heme oxygenase]] | + | [[Category: Large Structures]] |
| - | [[Category: Lee, W C]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Murphy, M E.P]] | + | [[Category: Lee WC]] |
| - | [[Category: Reniere, M L]] | + | [[Category: Murphy MEP]] |
| - | [[Category: Skaar, E P]] | + | [[Category: Reniere ML]] |
| - | [[Category: Beta-barrel]] | + | [[Category: Skaar EP]] |
| - | [[Category: Cobalt protoporphyrin ix]]
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| - | [[Category: Cytoplasm]]
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| - | [[Category: Heme]]
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| - | [[Category: Iron]]
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| - | [[Category: Metal-binding]]
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| - | [[Category: Monooxygenase]]
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| - | [[Category: Oxidoreductase]]
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| - | [[Category: Ruffling]]
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| Structural highlights
Function
HDOX2_STAAN Allows bacterial pathogens to use the host heme as an iron source. Catalyzes the oxidative degradation of the heme macrocyclic porphyrin ring to the oxo-bilirubin chromophore staphylobilin (a mixture of the linear tetrapyrroles 5-oxo-delta-bilirubin and 15-oxo-beta-bilirubin) in the presence of a suitable electron donor such as ascorbate or NADPH--cytochrome P450 reductase, with subsequent release of free iron.[HAMAP-Rule:MF_01272][1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
IsdG and IsdI are paralogous proteins that are intracellular components of a complex heme uptake system in Staphylococcus aureus. IsdG and IsdI were shown previously to reductively degrade hemin. Crystal structures of the apoproteins show that these proteins belong to a newly identified heme degradation family distinct from canonical eukaryotic and prokaryotic heme oxygenases. Here we report the crystal structures of an inactive N7A variant of IsdG in complex with Fe(3+)-protoporphyrin IX (IsdG-hemin) and of IsdI in complex with cobalt protoporphyrin IX (IsdI-CoPPIX) to 1.8 A or better resolution. These structures show that the metalloporphyrins are buried into similar deep clefts such that the propionic acids form salt bridges to two Arg residues. His(77) (IsdG) or His(76) (IsdI), a critical residue required for activity, is coordinated to the Fe(3+) or Co(3+) atoms, respectively. The bound porphyrin rings form extensive steric interactions in the binding cleft such that the rings are highly distorted from the plane. This distortion is best described as ruffled and places the beta- and delta-meso carbons proximal to the distal oxygen-binding site. In the IsdG-hemin structure, Fe(3+) is pentacoordinate, and the distal side is occluded by the side chain of Ile(55). However, in the structure of IsdI-CoPPIX, the distal side of the CoPPIX accommodates a chloride ion in a cavity formed through a conformational change in Ile(55). The chloride ion participates in a hydrogen bond to the side chain amide of Asn(6). Together the structures suggest a reaction mechanism in which a reactive peroxide intermediate proceeds with nucleophilic oxidation at the beta- or delta-meso carbon of the hemin.
Ruffling of metalloporphyrins bound to IsdG and IsdI, two heme-degrading enzymes in Staphylococcus aureus.,Lee WC, Reniere ML, Skaar EP, Murphy ME J Biol Chem. 2008 Nov 7;283(45):30957-63. Epub 2008 Aug 19. PMID:18713745[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lee WC, Reniere ML, Skaar EP, Murphy ME. Ruffling of metalloporphyrins bound to IsdG and IsdI, two heme-degrading enzymes in Staphylococcus aureus. J Biol Chem. 2008 Nov 7;283(45):30957-63. Epub 2008 Aug 19. PMID:18713745 doi:10.1074/jbc.M709486200
- ↑ Reniere ML, Ukpabi GN, Harry SR, Stec DF, Krull R, Wright DW, Bachmann BO, Murphy ME, Skaar EP. The IsdG-family of haem oxygenases degrades haem to a novel chromophore. Mol Microbiol. 2010 Mar;75(6):1529-38. Epub 2010 Feb 17. PMID:20180905 doi:10.1111/j.1365-2958.2010.07076.x
- ↑ Lee WC, Reniere ML, Skaar EP, Murphy ME. Ruffling of metalloporphyrins bound to IsdG and IsdI, two heme-degrading enzymes in Staphylococcus aureus. J Biol Chem. 2008 Nov 7;283(45):30957-63. Epub 2008 Aug 19. PMID:18713745 doi:10.1074/jbc.M709486200
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