4wkm: Difference between revisions
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==AmpR effector binding domain from Citrobacter freundii bound to UDP-MurNAc-pentapeptide== | ==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=''> | <StructureSection load='4wkm' size='340' side='right' caption='[[4wkm]], [[Resolution|resolution]] 2.15Å' scene=''> | ||
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><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></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><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></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kos|3kos]], [[3kot|3kot]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kos|3kos]], [[3kot|3kot]]</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=4wkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wkm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wkm RCSB], [http://www.ebi.ac.uk/pdbsum/4wkm PDBsum]</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=4wkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wkm OCA], [http://pdbe.org/4wkm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wkm RCSB], [http://www.ebi.ac.uk/pdbsum/4wkm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wkm ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4wkm" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 03:12, 26 January 2017
AmpR effector binding domain from Citrobacter freundii bound to UDP-MurNAc-pentapeptideAmpR effector binding domain from Citrobacter freundii bound to UDP-MurNAc-pentapeptide
Structural highlights
Publication Abstract from PubMedInducible 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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