View source for 9rgu


==Crystal Structure of Rattus norvegicus Enoyl-CoA Hydratase in complex with 3S hydroxyhexanoyl-PAN and 3',5', diphosphate adenosine==
<StructureSection load='9rgu' size='340' side='right'caption='[[9rgu]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9rgu]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9RGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9RGU FirstGlance]. <br>
</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1JF6:~{S}-[2-[3-[[(2~{R})-3,3-dimethyl-2,4-bis(oxidanyl)butanoyl]amino]propanoylamino]ethyl]+(3~{S})-3-oxidanylhexanethioate'>A1JF6</scene>, <scene name='pdbligand=A3P:ADENOSINE-3-5-DIPHOSPHATE'>A3P</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</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=9rgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9rgu OCA], [https://pdbe.org/9rgu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9rgu RCSB], [https://www.ebi.ac.uk/pdbsum/9rgu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9rgu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ECHM_RAT ECHM_RAT] Straight-chain enoyl-CoA thioesters from C4 up to at least C16 are processed, although with decreasing catalytic rate.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Thioester chemistry is exploited in Nature by many CoA-dependent enzymes. However, the covalent nature of CoA attachment largely prevents the use of these enzymes in many applications. Replacing the CoA moiety with simpler, truncated fragments, such as its pantetheine (PAN) moiety, is also hampered by the lack of understanding of the function of the CoA moiety in enzymatic conversions. Herein, we describe the utilization of the enzyme (2E)-enoyl-CoA hydratase (ECH) using PAN thioesters and an activator, 3',5'-ADP (PAP). ECH catalyzes the hydration of the carbon-carbon double bond of (2E)-enoyl-CoA substrates in the beta-oxidation lipid-degrading pathway. The hydration reaction is very challenging to carry out by traditional chemical synthesis, as no selective catalysts are available. Structural enzymology of ECH and its complexes with (3S)-hydroxyacyl-CoA products show that hydrogen bonds between the adenine 6-amino group of the ADP moiety of CoA and loop-2 induce a small structural change in this active site loop, tightening the NN distance between the hydrogen bond donors of the oxyanion hole from 5.2 A (unliganded) to 4.0 A and forming a competent oxyanion hole at the catalytic site. A structurally similar and catalytically competent oxyanion hole is observed in the complex with (3S)-hydroxyhexanoyl PAN and the activator 3',5'-ADP, both bound at the active site. The use of 3',5'-ADP as the activator enables the synthetic use of ECH for the hydration of a wide range of (2E)-enoyl-PAN substrates with different steric demands and functionalities. The products, 3-hydroxyacyl-PAN thioesters, were obtained in good isolated yields and excellent stereoselectivities (typically &gt;99:&lt;1 3S:3R). Even for acyl chains that contain reactive groups such as bromide or methyl ester functionalities at C7, no side products resulting from potentially competing cyclization could be detected in the enzymatic hydration protocol.

Enantioselective Hydration of Non-CoA Enoyl-Thioesters by Enoyl-CoA Hydratase (ECH): Activation of the Active Site Oxyanion Hole with 3',5'-Adenosine-Diphosphate Enables Competent Catalysis.,Dalwani S, Mondal PK, Schmitz W, Wierenga RK, Pihko PM JACS Au. 2026 Mar 23;6(4):2464-2472. doi: 10.1021/jacsau.6c00054. eCollection , 2026 Apr 27. PMID:42063829<ref>PMID:42063829</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9rgu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Dalwani S]]
[[Category: Wierenga RK]]