View source for 4fnh


==Crystal structure of IsdI-W66Y in complex with heme==
<StructureSection load='4fnh' size='340' side='right'caption='[[4fnh]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4fnh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_N315 Staphylococcus aureus subsp. aureus N315]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FNH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FNH 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=4fnh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fnh OCA], [https://pdbe.org/4fnh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fnh RCSB], [https://www.ebi.ac.uk/pdbsum/4fnh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fnh ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
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== Publication Abstract from PubMed ==
IsdG and IsdI are paralogous heme degrading enzymes from the bacterium Staphylococcus aureus. Heme bound by these enzymes is extensively ruffled such that the meso-carbons at the sites of oxidation are distorted toward bound oxygen. In contrast, the canonical heme oxygenase family degrades heme that is bound with minimal distortion. Trp-66 is a conserved heme pocket residue in IsdI implicated in heme ruffling. IsdI variants with Trp-66 replaced with residues having less bulky aromatic and alkyl side chains were characterized with respect to catalytic activity, heme ruffling, and electrochemical properties. The heme degradation activity of the W66Y and W66F variants was approximately half that of the wild-type enzyme, whereas the W66L and W66A variants were inactive. A crystal structure and NMR spectroscopic analysis of the W66Y variant reveals that heme binds to this enzyme with less heme ruffling than observed for wild-type IsdI. The reduction potential of this variant (-96 +/- 7 mV versus standard hydrogen electrode) is similar to that of wild-type IsdI (-89 +/- 7 mV), so we attribute the diminished activity of this variant to the diminished heme ruffling observed for heme bound to this enzyme and conclude that Trp-66 is required for optimal catalytic activity.

Inactivation of the Heme Degrading Enzyme IsdI by an Active Site Substitution That Diminishes Heme Ruffling.,Ukpabi G, Takayama SJ, Mauk AG, Murphy ME J Biol Chem. 2012 Oct 5;287(41):34179-88. doi: 10.1074/jbc.M112.393249. Epub 2012, Aug 13. PMID:22891243<ref>PMID:22891243</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4fnh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Heme oxygenase 3D structures|Heme oxygenase 3D structures]]
*[[Monooxygenase 3D structures|Monooxygenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus subsp. aureus N315]]
[[Category: Murphy MEP]]
[[Category: Ukpabi GN]]