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4ubt

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Structure of the C93S variant of the 3-ketoacyl-CoA thiolase FadA5 from M. tuberculosis in complex with a steroid and CoA.

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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ubt"

Categories: Large Structures | Mycobacterium tuberculosis H37Rv | Kisker C | Schaefer CM

@@ Line 1: / Line 1: @@
 ==Structure of the C93S variant of the 3-ketoacyl-CoA thiolase FadA5 from M. tuberculosis in complex with a steroid and CoA.==
-<StructureSection load='4ubt' size='340' side='right' caption='[[4ubt]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+<StructureSection load='4ubt' size='340' side='right'caption='[[4ubt]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ubt]] is a 4 chain structure. 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]] 1.7&#8491;</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='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='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://www.rcsb.org/pdb/explore.do?structureId=4ubt RCSB], [http://www.ebi.ac.uk/pdbsum/4ubt PDBsum]</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>
 </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;">
 == Publication Abstract from PubMed ==
@@ Line 15: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4ubt" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Thiolase 3D structures|Thiolase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Acetyl-CoA C-acyltransferase]]
+[[Category: Large Structures]]
-[[Category: Kisker, C]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Schaefer, C M]]
+[[Category: Kisker C]]
-[[Category: Degradative thiolase]]
+[[Category: Schaefer CM]]
-[[Category: Steroid-complex]]
-[[Category: Transferase]]

4ubt

From Proteopedia

Current revision

Structure of the C93S variant of the 3-ketoacyl-CoA thiolase FadA5 from M. tuberculosis in complex with a steroid and CoA.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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