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==Crystal structure of S. aureus FabI inhibited by SKTS1==
<StructureSection load='6yur' size='340' side='right'caption='[[6yur]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6yur]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YUR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YUR 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]] 1.96&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F9T:6-[4-(4-hexyl-2-oxidanyl-phenoxy)phenoxy]pyridin-2-ol'>F9T</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=6yur FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yur OCA], [https://pdbe.org/6yur PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yur RCSB], [https://www.ebi.ac.uk/pdbsum/6yur PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yur ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FABI_STAA8 FABI_STAA8] Catalyzes the reduction of a carbon-carbon double bond in an enoyl moiety that is covalently linked to an acyl carrier protein (ACP). It has a preference for a long chain (C12) substrate compared to the shorter (C4) acyl group. Involved in the elongation cycle of fatty acid which are used in the lipid metabolism (By similarity).<ref>PMID:18335995</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The enoyl-acyl carrier protein (ACP) reductase (ENR) is a key enzyme within the bacterial fatty-acid synthesis pathway. It has been demonstrated that small-molecule inhibitors carrying the diphenylether (DPE) scaffold bear a great potential for the development of highly specific and effective drugs against this enzyme class. Interestingly, different substitution patterns of the DPE scaffold have been shown to lead to varying effects on the kinetic and thermodynamic behavior toward ENRs from different organisms. Here, we investigated the effect of a 4'-pyridone substituent in the context of the slow tight-binding inhibitor SKTS1 on the inhibition of the Staphylococcus aureus enoyl-ACP-reductase saFabI and the closely related isoenzyme from Mycobacterium tuberculosis, InhA, and explored a new interaction site of DPE inhibitors within the substrate-binding pocket. Using high-resolution crystal structures of both complexes in combination with molecular dynamics (MD) simulations, kinetic measurements, and quantum mechanical (QM) calculations, we provide evidence that the 4'-pyridone substituent adopts different tautomeric forms when bound to the two ENRs. We furthermore elucidate the structural determinants leading to significant differences in the residence time of SKTS1 on both enzymes.

A Long Residence Time Enoyl-Reductase Inhibitor Explores an Extended Binding Region with Isoenzyme-Dependent Tautomer Adaptation and Differential Substrate-Binding Loop Closure.,Eltschkner S, Kehrein J, Le TA, Davoodi S, Merget B, Basak S, Weinrich JD, Schiebel J, Tonge PJ, Engels B, Sotriffer C, Kisker C ACS Infect Dis. 2021 Mar 12. doi: 10.1021/acsinfecdis.0c00437. PMID:33710875<ref>PMID:33710875</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6yur" style="background-color:#fffaf0;"></div>

==See Also==
*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Davoodi S]]
[[Category: Eltschkner S]]
[[Category: Engels B]]
[[Category: Kehrein J]]
[[Category: Kisker C]]
[[Category: Le TA]]
[[Category: Merget B]]
[[Category: Schiebel J]]
[[Category: Sotriffer CA]]
[[Category: Tonge PJ]]
[[Category: Weinrich JD]]