3mzf: Difference between revisions
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< | ==Structure of penicillin-binding protein 5 from E. coli: imipenem acyl-enzyme complex== | ||
<StructureSection load='3mzf' size='340' side='right'caption='[[3mzf]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | |||
or the | <table><tr><td colspan='2'>[[3mzf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MZF 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]] 1.5Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IM2:(5R)-5-[(1S,2R)-1-FORMYL-2-HYDROXYPROPYL]-3-[(2-{[(E)-IMINOMETHYL]AMINO}ETHYL)SULFANYL]-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>IM2</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=3mzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mzf OCA], [https://pdbe.org/3mzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mzf RCSB], [https://www.ebi.ac.uk/pdbsum/3mzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mzf ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DACA_ECOLI DACA_ECOLI] Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Penicillin-binding proteins (PBPs) are the molecular targets for the widely used beta-lactam class of antibiotics, but how these compounds act at the molecular level is not fully understood. We have determined crystal structures of Escherichia coli PBP 5 as covalent complexes with imipenem, cloxacillin, and cefoxitin. These antibiotics exhibit very different second-order rates of acylation for the enzyme. In all three structures, there is excellent electron density for the central portion of the beta-lactam, but weak or absent density for the R1 or R2 side chains. Areas of contact between the antibiotics and PBP 5 do not correlate with the rates of acylation. The same is true for conformational changes, because although a shift of a loop leading to an electrostatic interaction between Arg248 and the beta-lactam carboxylate, which occurs completely with cefoxitin and partially with imipenem and is absent with cloxacillin, is consistent with the different rates of acylation, mutagenesis of Arg248 decreased the level of cefoxitin acylation only 2-fold. Together, these data suggest that structures of postcovalent complexes of PBP 5 are unlikely to be useful vehicles for the design of new covalent inhibitors of PBPs. Finally, superimposition of the imipenem-acylated complex with PBP 5 in complex with a boronic acid peptidomimetic shows that the position corresponding to the hydrolytic water molecule is occluded by the ring nitrogen of the beta-lactam. Because the ring nitrogen occupies a similar position in all three complexes, this supports the hypothesis that deacylation is blocked by the continued presence of the leaving group after opening of the beta-lactam ring. | |||
Crystal structures of covalent complexes of beta-lactam antibiotics with Escherichia coli penicillin-binding protein 5: toward an understanding of antibiotic specificity.,Nicola G, Tomberg J, Pratt RF, Nicholas RA, Davies C Biochemistry. 2010 Sep 21;49(37):8094-104. PMID:20726582<ref>PMID:20726582</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3mzf" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Escherichia coli K-12]] | ||
[[ | [[Category: Large Structures]] | ||
[[Category: Davies C]] | |||
== | [[Category: Nicholas RA]] | ||
< | [[Category: Nicola G]] | ||
[[Category: Escherichia coli]] | [[Category: Pratt RF]] | ||
[[Category: Davies | [[Category: Tomberg J]] | ||
[[Category: Nicholas | |||
[[Category: Nicola | |||
[[Category: Pratt | |||
[[Category: Tomberg | |||
Latest revision as of 12:05, 6 September 2023
Structure of penicillin-binding protein 5 from E. coli: imipenem acyl-enzyme complexStructure of penicillin-binding protein 5 from E. coli: imipenem acyl-enzyme complex
Structural highlights
FunctionDACA_ECOLI Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors. Publication Abstract from PubMedPenicillin-binding proteins (PBPs) are the molecular targets for the widely used beta-lactam class of antibiotics, but how these compounds act at the molecular level is not fully understood. We have determined crystal structures of Escherichia coli PBP 5 as covalent complexes with imipenem, cloxacillin, and cefoxitin. These antibiotics exhibit very different second-order rates of acylation for the enzyme. In all three structures, there is excellent electron density for the central portion of the beta-lactam, but weak or absent density for the R1 or R2 side chains. Areas of contact between the antibiotics and PBP 5 do not correlate with the rates of acylation. The same is true for conformational changes, because although a shift of a loop leading to an electrostatic interaction between Arg248 and the beta-lactam carboxylate, which occurs completely with cefoxitin and partially with imipenem and is absent with cloxacillin, is consistent with the different rates of acylation, mutagenesis of Arg248 decreased the level of cefoxitin acylation only 2-fold. Together, these data suggest that structures of postcovalent complexes of PBP 5 are unlikely to be useful vehicles for the design of new covalent inhibitors of PBPs. Finally, superimposition of the imipenem-acylated complex with PBP 5 in complex with a boronic acid peptidomimetic shows that the position corresponding to the hydrolytic water molecule is occluded by the ring nitrogen of the beta-lactam. Because the ring nitrogen occupies a similar position in all three complexes, this supports the hypothesis that deacylation is blocked by the continued presence of the leaving group after opening of the beta-lactam ring. Crystal structures of covalent complexes of beta-lactam antibiotics with Escherichia coli penicillin-binding protein 5: toward an understanding of antibiotic specificity.,Nicola G, Tomberg J, Pratt RF, Nicholas RA, Davies C Biochemistry. 2010 Sep 21;49(37):8094-104. PMID:20726582[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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