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[[ | ==Crystal structure of S. aureus FabI in complex with NADP and 5-ethyl- 2-phenoxyphenol== | ||
<StructureSection load='4alk' size='340' side='right' caption='[[4alk]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4alk]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ALK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ALK FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E9P:5-ETHYL-2-PHENOXYPHENOL'>E9P</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ali|4ali]], [[4alj|4alj]], [[4all|4all]], [[4alm|4alm]], [[4aln|4aln]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADPH,_B-specific) Enoyl-[acyl-carrier-protein] reductase (NADPH, B-specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.10 1.3.1.10] </span></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=4alk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4alk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4alk RCSB], [http://www.ebi.ac.uk/pdbsum/4alk PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Methicillin-resistant Staphylococcus aureus (MRSA) infections constitute a serious health threat worldwide, and novel antibiotics are therefore urgently needed. The enoyl-ACP reductase (saFabI) is essential for the S. aureus fatty acid biosynthesis and, hence, serves as an attractive drug target. We have obtained a series of snapshots of this enzyme that provide a mechanistic picture of ligand and inhibitor binding, including a dimer-tetramer transition combined with extensive conformational changes. Significantly, our results reveal key differences in ligand binding and recognition compared to orthologous proteins. The remarkable observed protein flexibility rationalizes our finding that saFabI is capable of efficiently reducing branched-chain fatty acid precursors. Importantly, branched-chain fatty acids represent a major fraction of the S. aureus cell membrane and are crucial for its in vivo fitness. Our discovery thus addresses a long-standing controversy regarding the essentiality of the fatty acid biosynthesis pathway in S. aureus rationalizing saFabI as a drug target. | |||
Staphylococcus aureus FabI: Inhibition, Substrate Recognition, and Potential Implications for In Vivo Essentiality.,Schiebel J, Chang A, Lu H, Baxter MV, Tonge PJ, Kisker C Structure. 2012 May 9;20(5):802-13. PMID:22579249<ref>PMID:22579249</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Enoyl-Acyl-Carrier Protein Reductase|Enoyl-Acyl-Carrier Protein Reductase]] | *[[Enoyl-Acyl-Carrier Protein Reductase|Enoyl-Acyl-Carrier Protein Reductase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
[[Category: Chang, A | [[Category: Chang, A]] | ||
[[Category: Kisker, C | [[Category: Kisker, C]] | ||
[[Category: Schiebel, J | [[Category: Schiebel, J]] | ||
[[Category: Tonge, P J | [[Category: Tonge, P J]] | ||
[[Category: Fabi]] | [[Category: Fabi]] | ||
[[Category: Fatty acid biosynthesis]] | [[Category: Fatty acid biosynthesis]] | ||
Revision as of 13:56, 4 January 2015
Crystal structure of S. aureus FabI in complex with NADP and 5-ethyl- 2-phenoxyphenolCrystal structure of S. aureus FabI in complex with NADP and 5-ethyl- 2-phenoxyphenol
Structural highlights
Publication Abstract from PubMedMethicillin-resistant Staphylococcus aureus (MRSA) infections constitute a serious health threat worldwide, and novel antibiotics are therefore urgently needed. The enoyl-ACP reductase (saFabI) is essential for the S. aureus fatty acid biosynthesis and, hence, serves as an attractive drug target. We have obtained a series of snapshots of this enzyme that provide a mechanistic picture of ligand and inhibitor binding, including a dimer-tetramer transition combined with extensive conformational changes. Significantly, our results reveal key differences in ligand binding and recognition compared to orthologous proteins. The remarkable observed protein flexibility rationalizes our finding that saFabI is capable of efficiently reducing branched-chain fatty acid precursors. Importantly, branched-chain fatty acids represent a major fraction of the S. aureus cell membrane and are crucial for its in vivo fitness. Our discovery thus addresses a long-standing controversy regarding the essentiality of the fatty acid biosynthesis pathway in S. aureus rationalizing saFabI as a drug target. Staphylococcus aureus FabI: Inhibition, Substrate Recognition, and Potential Implications for In Vivo Essentiality.,Schiebel J, Chang A, Lu H, Baxter MV, Tonge PJ, Kisker C Structure. 2012 May 9;20(5):802-13. PMID:22579249[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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