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| | <StructureSection load='6ple' size='340' side='right'caption='[[6ple]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='6ple' size='340' side='right'caption='[[6ple]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ple]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PLE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PLE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ple]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PLE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PLE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BLA:BILIVERDINE+IX+ALPHA'>BLA</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]] 2.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mhuD, Rv3592 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BLA:BILIVERDINE+IX+ALPHA'>BLA</scene></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_(mycobilin-producing) Heme oxygenase (mycobilin-producing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.57 1.14.99.57] </span></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=6ple FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ple OCA], [https://pdbe.org/6ple PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ple RCSB], [https://www.ebi.ac.uk/pdbsum/6ple PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ple ProSAT]</span></td></tr> |
| - | <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=6ple FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ple OCA], [http://pdbe.org/6ple PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ple RCSB], [http://www.ebi.ac.uk/pdbsum/6ple PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ple ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MHUD_MYCTU MHUD_MYCTU]] Catalyzes the oxidative degradation of the heme macrocyclic porphyrin ring in the presence of a suitable electron donor such as ascorbate or NADPH--cytochrome P450 reductase, with subsequent release of free iron. | + | [https://www.uniprot.org/uniprot/MHUD_MYCTU MHUD_MYCTU] Catalyzes the oxidative degradation of the heme macrocyclic porphyrin ring in the presence of a suitable electron donor such as ascorbate or NADPH--cytochrome P450 reductase, with subsequent release of free iron. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6ple" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6ple" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Heme oxygenase 3D structures|Heme oxygenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Chao, A]] | + | [[Category: Chao A]] |
| - | [[Category: Goulding, C W]] | + | [[Category: Goulding CW]] |
| - | [[Category: Biliverdin]]
| + | |
| - | [[Category: Cell wall]]
| + | |
| - | [[Category: Heme binding]]
| + | |
| - | [[Category: Heme catabolic process]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Metal ion binding]]
| + | |
| - | [[Category: Monooxygenase activity]]
| + | |
| - | [[Category: Oxidation reduction process]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Oxidoreductase activity]]
| + | |
| - | [[Category: Plasma membrane]]
| + | |
| Structural highlights
Function
MHUD_MYCTU Catalyzes the oxidative degradation of the heme macrocyclic porphyrin ring in the presence of a suitable electron donor such as ascorbate or NADPH--cytochrome P450 reductase, with subsequent release of free iron.
Publication Abstract from PubMed
Mycobacterium tuberculosis(Mtb), the causative agent of tuberculosis, requires iron for survival. In Mtb, MhuD is the cytosolic protein that degrades imported heme. MhuD is distinct, both in sequence and structure, from canonical heme oxygenases (HOs) but homologous with IsdG-type proteins. Canonical HO is found mainly in eukaryotes, while IsdG-type proteins are predominantly found in prokaryotes including pathogens. While there are several published structures of MhuD and other IsdG-type proteins in complex with heme substrate, no structures have been reported of IsdG-type proteins in complex with product, unlike HOs. We recently showed that the Mtb variant MhuD-R26S produces biliverdin IXalpha (alphaBV) rather than the wild-type mycobilin isomers as product. Given that mycobilin and other IsdG-type protein products like staphylobilin are difficult to isolate in quantities sufficient for structure determination, here we use the MhuD-R26S variant and its product alphaBV as a proxy to study the IsdG-type protein/product complex. First we show that alphaBV has nanomolar affinity for MhuD and the R26S variant. Second we determined the MhuD-R26S-BV complex structure to 2.5 A, which reveals two notable features (1) two alphaBV molecules bound per active site and (2) a novel alpha-helix (alpha3) unobserved in previous MhuD-heme structures. Finally, through molecular dynamics simulations we show that alpha3 is stable with the proximal alphaBV alone. With MhuD's high affinity for product along with observed structural and electrostatic changes that accompany substrate turnover suggest that there may be an unidentified class of proteins responsible for product extraction from MhuD and other IsdG-type proteins.
The structure of a Mycobacterium tuberculosis heme-degrading protein, MhuD, variant in complex with its product.,Chao A, Burley K, Sieminski PJ, de Miranda R, Chen X, Mobley DL, Goulding C Biochemistry. 2019 Oct 22. doi: 10.1021/acs.biochem.9b00726. PMID:31638374[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chao A, Burley K, Sieminski PJ, de Miranda R, Chen X, Mobley DL, Goulding C. The structure of a Mycobacterium tuberculosis heme-degrading protein, MhuD, variant in complex with its product. Biochemistry. 2019 Oct 22. doi: 10.1021/acs.biochem.9b00726. PMID:31638374 doi:http://dx.doi.org/10.1021/acs.biochem.9b00726
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