6ok1

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<StructureSection load='6ok1' size='340' side='right'caption='[[6ok1]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
<StructureSection load='6ok1' size='340' side='right'caption='[[6ok1]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6ok1]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OK1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OK1 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6ok1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermomonospora_curvata_DSM_43183 Thermomonospora curvata DSM 43183]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OK1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OK1 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</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>
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<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=6ok1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ok1 OCA], [http://pdbe.org/6ok1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ok1 RCSB], [http://www.ebi.ac.uk/pdbsum/6ok1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ok1 ProSAT]</span></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ok1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ok1 OCA], [https://pdbe.org/6ok1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ok1 RCSB], [https://www.ebi.ac.uk/pdbsum/6ok1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ok1 ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/LTP2_THECD LTP2_THECD] Probably involved in bile acid degradation (Probable). In vitro, when associated with the ChsH1/ChsH2 hydratase, catalyzes the retroaldol cleavage of 17-hydroxy-3-oxo-4-pregnene-20-carboxyl-CoA (17-HOPC-CoA), forming androst-4-ene-3,17-dione and propionyl-CoA (PubMed:31209106). The in vivo substrate is probably a closely analogous bile acid degradation metabolite (Probable).<ref>PMID:31209106</ref> <ref>PMID:31209106</ref>
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An aldolase from the bile acid-degrading actinobacterium Thermomonospora curvata catalyzes the C-C bond cleavage of an isopropyl-CoA side chain from the D-ring of the steroid metabolite 17-hydroxy-3-oxo-4-pregnene-20-carboxyl-CoA (17-HOPC-CoA). Like its homolog from Mycobacterium tuberculosis, the T. curvata aldolase is a protein complex of Ltp2 with a DUF35 domain derived from the C-terminal domain of a hydratase (ChsH2DUF35) that catalyzes the preceding step in the pathway. We determined the structure of the Ltp2-ChsH2DUF35 complex at 1.7 A resolution using zinc-single anomalous diffraction (zinc-SAD). The enzyme adopts an alphabetabetaalpha organization, with the two Ltp2 protomers forming a central dimer, and the two ChsH2DUF35 protomers being at the periphery. Docking experiments suggested that Ltp2 forms a tight complex with the hydratase, but that each enzyme retains an independent CoA-binding site. Ltp2 adopted a fold similar to those in thiolases; however, instead of forming a deep tunnel, the Ltp2 active site formed an elongated cleft large enough to accommodate 17-HOPC-CoA. The active site lacked the two cysteines that served as the nucleophile and general base in thiolases and replaced a pair of oxyanion-hole histidine residues with Tyr-246 and Tyr-344. Phenylalanine replacement of either of these residues decreased aldolase catalytic activity at least 400-fold. On the basis of a 17-HOPC-CoA-docked model, we propose a catalytic mechanism where Tyr-294 acts as the general base abstracting a proton from the D-ring hydroxyl of 17-HOPC-CoA and Tyr-344 as the general acid that protonates the propionyl-CoA anion following C-C bond cleavage.
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The steroid side chain-cleaving aldolase Ltp2-ChsH2DUF35 is a thiolase superfamily member with a radically repurposed active site.,Aggett R, Mallette E, Gilbert SE, Vachon MA, Schroeter KL, Kimber MS, Seah SYK J Biol Chem. 2019 Jun 16. pii: RA119.008889. doi: 10.1074/jbc.RA119.008889. PMID:31209106<ref>PMID:31209106</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6ok1" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Aggett, R]]
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[[Category: Thermomonospora curvata DSM 43183]]
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[[Category: Kimber, M S]]
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[[Category: Aggett R]]
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[[Category: Mallette, E]]
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[[Category: Kimber MS]]
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[[Category: Seah, S Y.K]]
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[[Category: Mallette E]]
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[[Category: Aldolase]]
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[[Category: Seah SYK]]
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[[Category: Cholesterol degradation]]
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[[Category: Duf35 domain]]
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[[Category: Thiolase superfamily]]
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[[Category: Transport protein]]
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Current revision

Ltp2-ChsH2(DUF35) aldolase

PDB ID 6ok1

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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