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| | <StructureSection load='7lgb' size='340' side='right'caption='[[7lgb]], [[Resolution|resolution]] 2.21Å' scene=''> | | <StructureSection load='7lgb' size='340' side='right'caption='[[7lgb]], [[Resolution|resolution]] 2.21Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7lgb]] is a 1 chain structure with sequence from [https://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=7LGB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LGB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7lgb]] is a 1 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=7LGB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LGB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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]] 2.21Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fabG_8, fabG_1, fabG_2, fabG_4, fabG_6, fabG_7, DSI38_08445, E5M52_16205, ERS007665_00489, ERS007670_00458, ERS007679_00994, ERS007681_00640, ERS007741_01258, ERS013471_03025, ERS023446_03243, ERS024276_00059, ERS075361_03673, F6W99_02176, FRD82_16680, SAMEA2683035_03264 ([https://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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=7lgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lgb OCA], [https://pdbe.org/7lgb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lgb RCSB], [https://www.ebi.ac.uk/pdbsum/7lgb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lgb ProSAT]</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=7lgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lgb OCA], [https://pdbe.org/7lgb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lgb RCSB], [https://www.ebi.ac.uk/pdbsum/7lgb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lgb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CHSB1_MYCTU CHSB1_MYCTU] A reversible dehydrogenase involved in cholesterol side-chain degradation. Catalyzes the oxidation of hydroxyl-cholesterol-CoA ester metabolic intermediate (22S)-HOCO-CoA (3-oxo-chol-4-ene-(22S)-hydroxy-24-oyl-CoA), the product of ChsH3, has no activity on (22R)-HOCO-CoA (the product of EchA19). Also acts on (3R)-hydroxyoctanoyl-CoA and 17-beta-hydroxyandrost-4-en-3-one, but not on 7-alpha-hydroxyandrost-4-en-3-one, uses NAD(+) but not NADP(+).<ref>PMID:33826843</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Garcia-Diaz, M]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Sampson, N S]] | + | [[Category: Garcia-Diaz M]] |
| - | [[Category: Werman, J M]] | + | [[Category: Sampson NS]] |
| - | [[Category: Yang, M]] | + | [[Category: Werman JM]] |
| - | [[Category: Yin, X]] | + | [[Category: Yang M]] |
| - | [[Category: Yuan, T]] | + | [[Category: Yin X]] |
| - | [[Category: Oxidoreductase]]
| + | [[Category: Yuan T]] |
| - | [[Category: Short-chain type alcohol dehydrogenase/reductase hydroxyacyl-coa dehydrogenase]]
| + | |
| Structural highlights
Function
CHSB1_MYCTU A reversible dehydrogenase involved in cholesterol side-chain degradation. Catalyzes the oxidation of hydroxyl-cholesterol-CoA ester metabolic intermediate (22S)-HOCO-CoA (3-oxo-chol-4-ene-(22S)-hydroxy-24-oyl-CoA), the product of ChsH3, has no activity on (22R)-HOCO-CoA (the product of EchA19). Also acts on (3R)-hydroxyoctanoyl-CoA and 17-beta-hydroxyandrost-4-en-3-one, but not on 7-alpha-hydroxyandrost-4-en-3-one, uses NAD(+) but not NADP(+).[1]
Publication Abstract from PubMed
The unique ability of Mycobacterium tuberculosis (Mtb) to utilize host lipids such as cholesterol for survival, persistence, and virulence has made the metabolic pathway of cholesterol an area of great interest for therapeutics development. Herein, we identify and characterize two genes from the Cho-region (genomic locus responsible for cholesterol catabolism) of the Mtb genome, chsH3 (Rv3538) and chsB1 (Rv3502c). Their protein products catalyze two sequential stereospecific hydration and dehydrogenation steps in the beta-oxidation of the cholesterol side chain. ChsH3 favors the 22S hydration of 3-oxo-cholest-4,22-dien-24-oyl-CoA in contrast to the previously reported EchA19 (Rv3516), which catalyzes formation of the (22R)-hydroxy-3-oxo-cholest-4-en-24-oyl-CoA from the same enoyl-CoA substrate. ChsB1 is stereospecific and catalyzes dehydrogenation of the ChsH3 product but not the EchA19 product. The X-ray crystallographic structure of the ChsB1 apo-protein was determined at a resolution of 2.03 A, and the holo-enzyme with bound NAD(+) cofactor was determined at a resolution of 2.21 A. The homodimeric structure is representative of a classical NAD(+)-utilizing short-chain type alcohol dehydrogenase/reductase, including a Rossmann-fold motif, but exhibits a unique substrate binding site architecture that is of greater length and width than its homologous counterparts, likely to accommodate the bulky steroid substrate. Intriguingly, Mtb utilizes hydratases from the MaoC-like family in sterol side-chain catabolism in contrast to fatty acid beta-oxidation in other species that utilize the evolutionarily distinct crotonase family of hydratases.
Enzymatic beta-Oxidation of the Cholesterol Side Chain in Mycobacterium tuberculosis Bifurcates Stereospecifically at Hydration of 3-Oxo-cholest-4,22-dien-24-oyl-CoA.,Yuan T, Werman JM, Yin X, Yang M, Garcia-Diaz M, Sampson NS ACS Infect Dis. 2021 Apr 7. doi: 10.1021/acsinfecdis.1c00069. PMID:33826843[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yuan T, Werman JM, Yin X, Yang M, Garcia-Diaz M, Sampson NS. Enzymatic beta-Oxidation of the Cholesterol Side Chain in Mycobacterium tuberculosis Bifurcates Stereospecifically at Hydration of 3-Oxo-cholest-4,22-dien-24-oyl-CoA. ACS Infect Dis. 2021 Apr 7. doi: 10.1021/acsinfecdis.1c00069. PMID:33826843 doi:http://dx.doi.org/10.1021/acsinfecdis.1c00069
- ↑ Yuan T, Werman JM, Yin X, Yang M, Garcia-Diaz M, Sampson NS. Enzymatic beta-Oxidation of the Cholesterol Side Chain in Mycobacterium tuberculosis Bifurcates Stereospecifically at Hydration of 3-Oxo-cholest-4,22-dien-24-oyl-CoA. ACS Infect Dis. 2021 Apr 7. doi: 10.1021/acsinfecdis.1c00069. PMID:33826843 doi:http://dx.doi.org/10.1021/acsinfecdis.1c00069
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