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==AmpR effector binding domain from Citrobacter freundii bound to UDP-MurNAc-pentapeptide== | |||
<StructureSection load='4wkm' size='340' side='right'caption='[[4wkm]], [[Resolution|resolution]] 2.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4wkm]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Citrobacter_freundii_ATCC_8090_=_MTCC_1658_=_NBRC_12681 Citrobacter freundii ATCC 8090 = MTCC 1658 = NBRC 12681]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WKM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WKM 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]] 2.15Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=API:2,6-DIAMINOPIMELIC+ACID'>API</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=FGA:GAMMA-D-GLUTAMIC+ACID'>FGA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MUB:N-ACETYLMURAMIC+ACID'>MUB</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=4wkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wkm OCA], [https://pdbe.org/4wkm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wkm RCSB], [https://www.ebi.ac.uk/pdbsum/4wkm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wkm ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Inducible expression of chromosomal AmpC beta-lactamase is a major cause of beta-lactam antibiotic resistance in the Gram negative bacteria Pseudomonas aeruginosa and Enterobacteriaceae. AmpC expression is induced by the LysR-type transcriptional regulator (LTTR) AmpR, which activates ampC expression in response to changes in peptidoglycan (PG) metabolite levels that occur during exposure to beta-lactams. Under normal conditions, AmpR represses ampC transcription by binding the PG precursor UDP-MurNAc-pentapeptide. When exposed to beta-lactams however, PG catabolites (1,6-anhydroMurNAc-peptides) accumulate in the cytosol, which have been proposed to competitively displace UDP-MurNAcpentapeptide from AmpR and convert it into an activator of ampC transcription. Here we describe the molecular interactions between AmpR (from Citrobacter freundii), its DNA operator, and repressor UDP-MurNAcpentapeptide. Non-denaturing mass spectrometry revealed AmpR to be a homotetramer that is stabilized by DNA containing the T-N11-A LTTR binding motif, and that it can bind four repressor molecules in an apparently stepwise manner. A crystal structure of the AmpR effector-binding domain bound to UDP-MurNAc-pentapeptide revealed that the terminal D-Ala-D-Ala motif of the repressor forms the primary contacts with the protein. This observation supports previous claims that 1,6-anhydro-MurNAc-pentapeptide converts AmpR into an activator of ampC transcription more effectively than 1,6-anhydro-MurNAc-tripeptide (which lacks the D-Ala-D-Ala motif). Finally, small angle X-ray scattering demonstrates that the AmpR-DNA complex adopts a flat conformation similar to the LTTR protein AphB and undergoes only a slight conformational change when binding UDP-MurNAc-pentapeptide. Modeling the AmpR:DNA tetramer bound to UDP-MurNAcpentapeptide predicts that the UDP-MurNAc moiety of the repressor participates in modulating AmpR function. | |||
The beta-lactamase Gene Regulator AmpR is a Tetramer that Recognizes and Binds the D-Ala-D-Ala Motif of its Repressor UDP-MurNAc-pentapeptide.,Vadlamani G, Thomas MD, Patel TR, Donald LJ, Reeve TM, Stetefeld J, Standing KG, Vocadlo DJ, Mark BL J Biol Chem. 2014 Dec 5. pii: jbc.M114.618199. PMID:25480792<ref>PMID:25480792</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4wkm" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Transcriptional activator 3D structures|Transcriptional activator 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Citrobacter freundii ATCC 8090 = MTCC 1658 = NBRC 12681]] | |||
[[Category: Large Structures]] | |||
[[Category: Mark BL]] | |||
[[Category: Reeve TM]] | |||
[[Category: Vadlamani G]] | |||