1o07: Difference between revisions

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New page: left|200px<br /><applet load="1o07" size="450" color="white" frame="true" align="right" spinBox="true" caption="1o07, resolution 1.71Å" /> '''Crystal Structure of...
 
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[[Image:1o07.gif|left|200px]]<br /><applet load="1o07" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1o07, resolution 1.71&Aring;" />
'''Crystal Structure of the complex between Q120L/Y150E mutant of AmpC and a beta-lactam inhibitor (MXG)'''<br />


==Overview==
==Crystal Structure of the complex between Q120L/Y150E mutant of AmpC and a beta-lactam inhibitor (MXG)==
Penicillin-binding proteins (PBPs), biosynthetic enzymes of bacterial cell, wall assembly, and beta-lactamases, resistance enzymes to beta-lactam, antibiotics, are related to each other from an evolutionary point of view., Massova and Mobashery (Antimicrob. Agents Chemother. 1998, 42, 1-17) have, proposed that for beta-lactamases to have become effective at their, function as antibiotic resistance enzymes, they would have had to undergo, structure alterations such that they would not interact with the, peptidoglycan, which is the substrate for PBPs. A cephalosporin analogue, 7beta-[N-Acetyl-L-alanyl-gamma-D-glutamyl-L-lysine]-3-acetoxymethyl-3-ceph, em-carboxylic acid (compound 6), was conceived and synthesized to test, this notion. The X-ray structure of the complex of this cephalosporin, bound to the active site of the deacylation-deficient Q120L/Y150E variant, of the class C AmpC beta-lactamase from Escherichia coli was solved at, 1.71 A resolution. This complex revealed that the surface for interaction, with the strand of peptidoglycan that acylates the active site, which is, present in PBPs, is absent in the -lactamase active site. Furthermore, insertion of a peptide in the beta-lactamase active site at a location, where the second strand of peptidoglycan in some PBPs binds has, effectively abolished the possibility for such interaction with the, beta-lactamase. A 2.6 ns dynamics simulation was carried out for the, complex, which revealed that the peptidoglycan surrogate (i.e., the, active-site-bound ligand) undergoes substantial motion and is not, stabilized for binding within the active site. These factors taken, together disclose the set of structure modifications in the antibiotic, resistance enzyme that prevent it from interacting with the peptidoglycan, en route to achieving catalytic proficiency for their intended function.
<StructureSection load='1o07' size='340' side='right'caption='[[1o07]], [[Resolution|resolution]] 1.71&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1o07]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O07 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O07 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]] 1.71&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MXG:2-(1-{2-[4-(2-ACETYLAMINO-PROPIONYLAMINO)-4-CARBOXY-BUTYRYLAMINO]-6-AMINO-HEXANOYLAMINO}-2-OXO-ETHYL)-5-METHYLENE-5,6-DIHYDRO-2H-[1,3]THIAZINE-4-CARBOXYLIC+ACID'>MXG</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=1o07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o07 OCA], [https://pdbe.org/1o07 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o07 RCSB], [https://www.ebi.ac.uk/pdbsum/1o07 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o07 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o0/1o07_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1o07 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1O07 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with K and MXG as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1O07 OCA].
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Structural aspects for evolution of beta-lactamases from penicillin-binding proteins., Meroueh SO, Minasov G, Lee W, Shoichet BK, Mobashery S, J Am Chem Soc. 2003 Aug 13;125(32):9612-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12904027 12904027]
[[Category: Beta-lactamase]]
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Lee, W.]]
[[Category: Lee W]]
[[Category: Meroueh, S.O.]]
[[Category: Meroueh SO]]
[[Category: Minasov, G.]]
[[Category: Minasov G]]
[[Category: Mobashery, S.]]
[[Category: Mobashery S]]
[[Category: Shoichet, B.K.]]
[[Category: Shoichet BK]]
[[Category: K]]
[[Category: MXG]]
[[Category: beta-lactamase beta-lactam complex]]
[[Category: crystal structure]]
[[Category: enzyme inhibitor complex]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 22:42:00 2007''

Latest revision as of 11:00, 14 February 2024

Crystal Structure of the complex between Q120L/Y150E mutant of AmpC and a beta-lactam inhibitor (MXG)Crystal Structure of the complex between Q120L/Y150E mutant of AmpC and a beta-lactam inhibitor (MXG)

Structural highlights

1o07 is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.71Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1o07, resolution 1.71Å

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