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| | <StructureSection load='4nl5' size='340' side='right'caption='[[4nl5]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='4nl5' size='340' side='right'caption='[[4nl5]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4nl5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NL5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NL5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4nl5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NL5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NL5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CYN:CYANIDE+ION'>CYN</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> | + | </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=CYN:CYANIDE+ION'>CYN</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mhuD, MT3698, Rv3592 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=4nl5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nl5 OCA], [https://pdbe.org/4nl5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nl5 RCSB], [https://www.ebi.ac.uk/pdbsum/4nl5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nl5 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>
| + | |
| - | <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=4nl5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nl5 OCA], [http://pdbe.org/4nl5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nl5 RCSB], [http://www.ebi.ac.uk/pdbsum/4nl5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nl5 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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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Monooxygenase|Monooxygenase]] | + | *[[Monooxygenase 3D structures|Monooxygenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Heme oxygenase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chao, A]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Goulding, C W]] | + | [[Category: Chao A]] |
| - | [[Category: Morse, R P]] | + | [[Category: Goulding CW]] |
| - | [[Category: Beta barrel]] | + | [[Category: Morse RP]] |
| - | [[Category: Oxidoreductase]]
| + | |
| 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 heme utilization degrader (MhuD) is a heme-degrading protein from Mycobacterium tuberculosis responsible for extracting the essential nutrient iron from host-derived heme. MhuD has been previously shown to produce unique organic products compared to those of canonical heme oxygenases (HOs) as well as those of the IsdG/I heme-degrading enzymes from Staphylococcus aureus. Here, we report the X-ray crystal structure of cyanide-inhibited MhuD (MhuD-heme-CN) as well as detailed (1)H nuclear magnetic resonance (NMR), UV/vis absorption, and magnetic circular dichroism (MCD) spectroscopic characterization of this species. There is no evidence for an ordered network of water molecules on the distal side of the heme substrate in the X-ray crystal structure, as was previously reported for canonical HOs. The degree of heme ruffling in the crystal structure of MhuD is greater than that observed for HO and less than that observed for IsdI. As a consequence, the Fe 3dxz-, 3dyz-, and 3dxy-based MOs are very close in energy, and the room-temperature (1)H NMR spectrum of MhuD-heme-CN is consistent with population of both a (2)Eg electronic state with a (dxy)(2)(dxz,dyz)(3) electron configuration, similar to the ground state of canonical HOs, and a (2)B2g state with a (dxz,dyz)(4)(dxy)(1) electron configuration, similar to the ground state of cyanide-inhibited IsdI. Variable temperature, variable field MCD saturation magnetization data establishes that MhuD-heme-CN has a (2)B2g electronic ground state with a low-lying (2)Eg excited state. Our crystallographic and spectroscopic data suggest that there are both structural and electronic contributions to the alpha-meso regioselectivity of MhuD-catalyzed heme cleavage. The structural distortion of the heme substrate observed in the X-ray crystal structure of MhuD-heme-CN is likely to favor cleavage at the alpha- and gamma-meso carbons, whereas the spin density distribution may favor selective oxygenation of the alpha-meso carbon.
Crystallographic and Spectroscopic Insights into Heme Degradation by Mycobacterium tuberculosis MhuD.,Graves AB, Morse RP, Chao A, Iniguez A, Goulding CW, Liptak MD Inorg Chem. 2014 Jun 16;53(12):5931-40. doi: 10.1021/ic500033b. Epub 2014 Jun 5. PMID:24901029[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Graves AB, Morse RP, Chao A, Iniguez A, Goulding CW, Liptak MD. Crystallographic and Spectroscopic Insights into Heme Degradation by Mycobacterium tuberculosis MhuD. Inorg Chem. 2014 Jun 16;53(12):5931-40. doi: 10.1021/ic500033b. Epub 2014 Jun 5. PMID:24901029 doi:http://dx.doi.org/10.1021/ic500033b
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