4a0z: Difference between revisions
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==Structure of the global transcription regulator FapR from Staphylococcus aureus in complex with malonyl-CoA== | ==Structure of the global transcription regulator FapR from Staphylococcus aureus in complex with malonyl-CoA== | ||
<StructureSection load='4a0z' size='340' side='right' caption='[[4a0z]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='4a0z' size='340' side='right'caption='[[4a0z]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4a0z]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4a0z]] is a 2 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=4A0Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A0Z FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLC:MALONYL-COENZYME+A'>MLC</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4a0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a0z OCA], [https://pdbe.org/4a0z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a0z RCSB], [https://www.ebi.ac.uk/pdbsum/4a0z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a0z ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/Q2FZ56_STAA8 Q2FZ56_STAA8] Transcriptional factor involved in regulation of membrane lipid biosynthesis by repressing genes involved in fatty acid and phospholipid metabolism.[HAMAP-Rule:MF_01814] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 23: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Staphylococcus aureus]] | ||
[[Category: | [[Category: Albanesi D]] | ||
[[Category: | [[Category: Alzari PM]] | ||
[[Category: | [[Category: Buschiazzo A]] | ||
[[Category: | [[Category: Guerin ME]] | ||
[[Category: | [[Category: De Mendoza D]] | ||
Latest revision as of 14:17, 20 December 2023
Structure of the global transcription regulator FapR from Staphylococcus aureus in complex with malonyl-CoAStructure of the global transcription regulator FapR from Staphylococcus aureus in complex with malonyl-CoA
Structural highlights
FunctionQ2FZ56_STAA8 Transcriptional factor involved in regulation of membrane lipid biosynthesis by repressing genes involved in fatty acid and phospholipid metabolism.[HAMAP-Rule:MF_01814] Publication Abstract from PubMedThe biosynthesis of membrane lipids is an essential pathway for virtually all bacteria. Despite its potential importance for the development of novel antibiotics, little is known about the underlying signaling mechanisms that allow bacteria to control their membrane lipid composition within narrow limits. Recent studies disclosed an elaborate feed-forward system that senses the levels of malonyl-CoA and modulates the transcription of genes that mediate fatty acid and phospholipid synthesis in many Gram-positive bacteria including several human pathogens. A key component of this network is FapR, a transcriptional regulator that binds malonyl-CoA, but whose mode of action remains enigmatic. We report here the crystal structures of FapR from Staphylococcus aureus (SaFapR) in three relevant states of its regulation cycle. The repressor-DNA complex reveals that the operator binds two SaFapR homodimers with different affinities, involving sequence-specific contacts from the helix-turn-helix motifs to the major and minor grooves of DNA. In contrast with the elongated conformation observed for the DNA-bound FapR homodimer, binding of malonyl-CoA stabilizes a different, more compact, quaternary arrangement of the repressor, in which the two DNA-binding domains are attached to either side of the central thioesterase-like domain, resulting in a non-productive overall conformation that precludes DNA binding. The structural transition between the DNA-bound and malonyl-CoA-bound states of SaFapR involves substantial changes and large (>30 A) inter-domain movements; however, both conformational states can be populated by the ligand-free repressor species, as confirmed by the structure of SaFapR in two distinct crystal forms. Disruption of the ability of SaFapR to monitor malonyl-CoA compromises cell growth, revealing the essentiality of membrane lipid homeostasis for S. aureus survival and uncovering novel opportunities for the development of antibiotics against this major human pathogen. Structural Basis for Feed-Forward Transcriptional Regulation of Membrane Lipid Homeostasis in Staphylococcus aureus.,Albanesi D, Reh G, Guerin ME, Schaeffer F, Debarbouille M, Buschiazzo A, Schujman GE, de Mendoza D, Alzari PM PLoS Pathog. 2013 Jan;9(1):e1003108. doi: 10.1371/journal.ppat.1003108. Epub 2013, Jan 3. PMID:23300457[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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