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| | <StructureSection load='4ubt' size='340' side='right'caption='[[4ubt]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='4ubt' size='340' side='right'caption='[[4ubt]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ubt]] is a 4 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=4UBT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UBT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ubt]] is a 4 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=4UBT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UBT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3G6:(2S)-2-[(8S,9S,10R,13S,14S,17R)-10,13-DIMETHYL-3-OXO-2,3,6,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1H-CYCLOPENTA[A]PHENANTHREN-17-YL]PROPANOIC+ACID+(NON-PREFERRED+NAME)'>3G6</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 1.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fadA5, Rv3546, P425_03688, RVBD_3546 ([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=3G6:(2S)-2-[(8S,9S,10R,13S,14S,17R)-10,13-DIMETHYL-3-OXO-2,3,6,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1H-CYCLOPENTA[A]PHENANTHREN-17-YL]PROPANOIC+ACID+(NON-PREFERRED+NAME)'>3G6</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetyl-CoA_C-acyltransferase Acetyl-CoA C-acyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.16 2.3.1.16] </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=4ubt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ubt OCA], [https://pdbe.org/4ubt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ubt RCSB], [https://www.ebi.ac.uk/pdbsum/4ubt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ubt 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=4ubt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ubt OCA], [http://pdbe.org/4ubt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ubt RCSB], [http://www.ebi.ac.uk/pdbsum/4ubt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ubt ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/FADA5_MYCTU FADA5_MYCTU] Involved in the beta-oxidation of the cholesterol side chain (PubMed:19822655). It is important for utilization of cholesterol as a sole carbon source in vitro and for full virulence in the chronic stage of mouse lung infection (PubMed:19822655). Catalyzes the thiolysis of 3,22-dioxochol-4-en-24-oyl-CoA to yield 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA) and acetyl-CoA (PubMed:25482540). Also able to use acetoacetyl-CoA (AcAcCoA) as substrate (PubMed:19822655).<ref>PMID:19822655</ref> <ref>PMID:25482540</ref> |
| | <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== |
| - | *[[Thiolase|Thiolase]] | + | *[[Thiolase 3D structures|Thiolase 3D structures]] |
| - | *[[User:Karsten Theis/FadA5 thiolase|User:Karsten Theis/FadA5 thiolase]]
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Acetyl-CoA C-acyltransferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Kisker, C]] | + | [[Category: Kisker C]] |
| - | [[Category: Schaefer, C M]] | + | [[Category: Schaefer CM]] |
| - | [[Category: Degradative thiolase]]
| + | |
| - | [[Category: Steroid-complex]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
4ubt is a 4 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.7Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
FADA5_MYCTU Involved in the beta-oxidation of the cholesterol side chain (PubMed:19822655). It is important for utilization of cholesterol as a sole carbon source in vitro and for full virulence in the chronic stage of mouse lung infection (PubMed:19822655). Catalyzes the thiolysis of 3,22-dioxochol-4-en-24-oyl-CoA to yield 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA) and acetyl-CoA (PubMed:25482540). Also able to use acetoacetyl-CoA (AcAcCoA) as substrate (PubMed:19822655).[1] [2]
Publication Abstract from PubMed
With the exception of HIV, tuberculosis (TB) is the leading cause of mortality among infectious diseases. The urgent need to develop new antitubercular drugs is apparent due to the increasing number of drug-resistant Mycobacterium tuberculosis (Mtb) strains. Proteins involved in cholesterol import and metabolism have recently been discovered as potent targets against TB. FadA5, a thiolase from Mtb, is catalyzing the last step of the beta-oxidation reaction of the cholesterol side-chain degradation under release of critical metabolites and was shown to be of importance during the chronic stage of TB infections. To gain structural and mechanistic insight on FadA5, we characterized the enzyme in different stages of the cleavage reaction and with a steroid bound to the binding pocket. Structural comparisons to human thiolases revealed that it should be possible to target FadA5 specifically, and the steroid-bound structure provides a solid basis for the development of inhibitors against FadA5.
FadA5 a Thiolase from Mycobacterium tuberculosis: A Steroid-Binding Pocket Reveals the Potential for Drug Development against Tuberculosis.,Schaefer CM, Lu R, Nesbitt NM, Schiebel J, Sampson NS, Kisker C Structure. 2014 Dec 3. pii: S0969-2126(14)00355-4. doi:, 10.1016/j.str.2014.10.010. PMID:25482540[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nesbitt NM, Yang X, Fontan P, Kolesnikova I, Smith I, Sampson NS, Dubnau E. A thiolase of Mycobacterium tuberculosis is required for virulence and production of androstenedione and androstadienedione from cholesterol. Infect Immun. 2010 Jan;78(1):275-82. doi: 10.1128/IAI.00893-09. Epub 2009 Oct 12. PMID:19822655 doi:http://dx.doi.org/10.1128/IAI.00893-09
- ↑ Schaefer CM, Lu R, Nesbitt NM, Schiebel J, Sampson NS, Kisker C. FadA5 a Thiolase from Mycobacterium tuberculosis: A Steroid-Binding Pocket Reveals the Potential for Drug Development against Tuberculosis. Structure. 2014 Dec 3. pii: S0969-2126(14)00355-4. doi:, 10.1016/j.str.2014.10.010. PMID:25482540 doi:http://dx.doi.org/10.1016/j.str.2014.10.010
- ↑ Schaefer CM, Lu R, Nesbitt NM, Schiebel J, Sampson NS, Kisker C. FadA5 a Thiolase from Mycobacterium tuberculosis: A Steroid-Binding Pocket Reveals the Potential for Drug Development against Tuberculosis. Structure. 2014 Dec 3. pii: S0969-2126(14)00355-4. doi:, 10.1016/j.str.2014.10.010. PMID:25482540 doi:http://dx.doi.org/10.1016/j.str.2014.10.010
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