View source for 6tbb


==Crystal structure of S. aureus FabI in complex with NADPH and kalimantacin A (batumin)==
<StructureSection load='6tbb' size='340' side='right'caption='[[6tbb]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6tbb]] 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=6TBB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TBB 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]] 2.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KAL:Kalimantacin'>KAL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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=6tbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tbb OCA], [https://pdbe.org/6tbb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tbb RCSB], [https://www.ebi.ac.uk/pdbsum/6tbb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tbb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FABI_STAAR FABI_STAAR] Catalyzes the reduction of a carbon-carbon double bond in an enoyl moiety that is covalently linked to an acyl carrier protein (ACP). Involved in the elongation cycle of fatty acid which are used in the lipid metabolism (By similarity).
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== Publication Abstract from PubMed ==
The enoyl-acyl carrier protein reductase enzyme FabI is essential for fatty acid biosynthesis in Staphylococcus aureus and represents a promising target for the development of novel, urgently needed anti-staphylococcal agents. Here, we elucidate the mode of action of the kalimantacin antibiotics, a novel class of FabI inhibitors with clinically-relevant activity against multidrug-resistant S. aureus . By combining X-ray crystallography with molecular dynamics simulations, in vitro kinetic studies and chemical derivatization experiments, we characterize the interaction between the antibiotics and their target, and we demonstrate that the kalimantacins bind in a unique conformation that differs significantly from the binding mode of other known FabI inhibitors. We also investigate mechanisms of acquired resistance in S. aureus and identify key residues in FabI that stabilize the binding of the antibiotics. Our findings provide intriguing insights into the mode of action of a novel class of FabI inhibitors that will inspire future anti-staphylococcal drug development.

The kalimantacin polyketide antibiotics inhibit fatty acid biosynthesis in Staphylococcus aureus by targeting the enoyl-acyl carrier protein binding site of FabI.,Fage CD, Lathouwers T, Vanmeert M, Gao LJ, Vrancken K, Lammens EM, Weir A, Degroote R, Cuppens H, Kosol S, Simpson TJ, Crump MP, Willis CL, Herdewijn P, Lescrinier E, Lavigne R, Anne J, Masschelein J Angew Chem Int Ed Engl. 2020 Mar 24. doi: 10.1002/anie.201915407. PMID:32208550<ref>PMID:32208550</ref>

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

==See Also==
*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Fage CD]]
[[Category: Masschelein J]]