This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

6ok1

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Ltp2-ChsH2(DUF35) aldolase

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6ok1"

@@ Line 3: / Line 3: @@
 <StructureSection load='6ok1' size='340' side='right'caption='[[6ok1]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ok1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Thecd Thecd]. 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>
+<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>
-</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>
+</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tcur_3479 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=471852 THECD]), Tcur_3482 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=471852 THECD])</td></tr>
+<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>
-<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>
+<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>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[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>
-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.
-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>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 6ok1" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 22: / Line 15: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Thecd]]
+[[Category: Thermomonospora curvata DSM 43183]]
-[[Category: Aggett, R]]
+[[Category: Aggett R]]
-[[Category: Kimber, M S]]
+[[Category: Kimber MS]]
-[[Category: Mallette, E]]
+[[Category: Mallette E]]
-[[Category: Seah, S Y.K]]
+[[Category: Seah SYK]]
-[[Category: Aldolase]]
-[[Category: Cholesterol degradation]]
-[[Category: Duf35 domain]]
-[[Category: Thiolase superfamily]]
-[[Category: Transport protein]]

6ok1

From Proteopedia

Current revision

Ltp2-ChsH2(DUF35) aldolase

Structural highlights

Function

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox