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==Crystal structure of AmpC from E.coli with Enmetazobactam (AAI-101)==
==Crystal structure of AmpC from E.coli with Enmetazobactam (AAI-101)==
<StructureSection load='6t35' size='340' side='right'caption='[[6t35]]' scene=''>
<StructureSection load='6t35' size='340' side='right'caption='[[6t35]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T35 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6T35 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6t35]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T35 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T35 FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6t35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t35 OCA], [http://pdbe.org/6t35 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6t35 RCSB], [http://www.ebi.ac.uk/pdbsum/6t35 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6t35 ProSAT]</span></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=M9W:Enmetazobactam+derived+trans-enamine+adduct.'>M9W</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ampC, ampA, b4150, JW4111 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></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=6t35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t35 OCA], [https://pdbe.org/6t35 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t35 RCSB], [https://www.ebi.ac.uk/pdbsum/6t35 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t35 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI]] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
SignificanceMicrobial resistance to beta-lactam antibiotics mediated by beta-lactamase-catalyzed hydrolysis is a major global health concern. Penam sulfones, which are structurally related to penicillins, inhibit clinically important serine beta-lactamases (SBLs) by forming transiently stable covalent complexes, thereby protecting beta-lactam antibiotics from hydrolysis. The characterization of these complexes and mechanisms of SBL inhibition is important for development of new SBL inhibitors (SBLi). Studies on the mechanism of the new SBLi enmetazobactam employing mass spectrometry and X-ray crystallography inform on its mode of action and also lead to reevaluation of mechanisms of current clinically important SBLi. In addition to insights into the mechanisms of transient SBL inhibition by penam sulfones, the results reveal potential for penam sulfone optimization to enable irreversible SBL inhibition.
Studies on enmetazobactam clarify mechanisms of widely used beta-lactamase inhibitors.,Lang PA, Raj R, Tumber A, Lohans CT, Rabe P, Robinson CV, Brem J, Schofield CJ Proc Natl Acad Sci U S A. 2022 May 3;119(18):e2117310119. doi:, 10.1073/pnas.2117310119. Epub 2022 Apr 29. PMID:35486701<ref>PMID:35486701</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6t35" style="background-color:#fffaf0;"></div>
==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Beta-lactamase]]
[[Category: Ecoli]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Brem J]]
[[Category: Brem, J]]
[[Category: Lang PA]]
[[Category: Lang, P A]]
[[Category: Leissing TM]]
[[Category: Leissing, T M]]
[[Category: Schofield CJ]]
[[Category: Schofield, C J]]
[[Category: Antibiotic resistance]]
[[Category: Antimicrobial protein]]
[[Category: Beta lactamase]]
[[Category: Hydrolase]]
[[Category: Mechanism based inhibitor]]

Revision as of 09:23, 12 May 2022

Crystal structure of AmpC from E.coli with Enmetazobactam (AAI-101)Crystal structure of AmpC from E.coli with Enmetazobactam (AAI-101)

Structural highlights

6t35 is a 1 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , ,
Gene:ampC, ampA, b4150, JW4111 (ECOLI)
Activity:Beta-lactamase, with EC number 3.5.2.6
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.

Publication Abstract from PubMed

SignificanceMicrobial resistance to beta-lactam antibiotics mediated by beta-lactamase-catalyzed hydrolysis is a major global health concern. Penam sulfones, which are structurally related to penicillins, inhibit clinically important serine beta-lactamases (SBLs) by forming transiently stable covalent complexes, thereby protecting beta-lactam antibiotics from hydrolysis. The characterization of these complexes and mechanisms of SBL inhibition is important for development of new SBL inhibitors (SBLi). Studies on the mechanism of the new SBLi enmetazobactam employing mass spectrometry and X-ray crystallography inform on its mode of action and also lead to reevaluation of mechanisms of current clinically important SBLi. In addition to insights into the mechanisms of transient SBL inhibition by penam sulfones, the results reveal potential for penam sulfone optimization to enable irreversible SBL inhibition.

Studies on enmetazobactam clarify mechanisms of widely used beta-lactamase inhibitors.,Lang PA, Raj R, Tumber A, Lohans CT, Rabe P, Robinson CV, Brem J, Schofield CJ Proc Natl Acad Sci U S A. 2022 May 3;119(18):e2117310119. doi:, 10.1073/pnas.2117310119. Epub 2022 Apr 29. PMID:35486701[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Lang PA, Raj R, Tumber A, Lohans CT, Rabe P, Robinson CV, Brem J, Schofield CJ. Studies on enmetazobactam clarify mechanisms of widely used beta-lactamase inhibitors. Proc Natl Acad Sci U S A. 2022 May 3;119(18):e2117310119. doi:, 10.1073/pnas.2117310119. Epub 2022 Apr 29. PMID:35486701 doi:http://dx.doi.org/10.1073/pnas.2117310119

6t35, resolution 1.75Å

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