View source for 1pwg


==Covalent Penicilloyl Acyl Enzyme Complex Of The Streptomyces R61 DD-Peptidase With A Highly Specific Penicillin==
<StructureSection load='1pwg' size='340' side='right'caption='[[1pwg]], [[Resolution|resolution]] 1.07&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1pwg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp._R61 Streptomyces sp. R61]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PWG 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]] 1.074&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HE0:(2R,4S)-2-[(1R)-1-{[(6S)-6-CARBOXY-6-(GLYCYLAMINO)HEXANOYL]AMINO}-2-OXOETHYL]-5,5-DIMETHYL-1,3-THIAZOLIDINE-4-CARBOXYLIC+ACID'>HE0</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=1pwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pwg OCA], [https://pdbe.org/1pwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pwg RCSB], [https://www.ebi.ac.uk/pdbsum/1pwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pwg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DAC_STRSR DAC_STRSR] Catalyzes distinct carboxypeptidation and transpeptidation reactions during the last stages of wall peptidoglycan synthesis. Mistaking a beta-lactam antibiotic molecule for a normal substrate (i.e. a D-alanyl-D-alanine-terminated peptide), it becomes immobilized in the form of a long-lived, serine-ester-linked acyl enzyme and thus behave as penicillin-binding protein (PBP).
== 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/pw/1pwg_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=1pwg ConSurf].
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== Publication Abstract from PubMed ==
The bacterial D-alanyl-D-alanine transpeptidases (DD-peptidases) are the killing targets of beta-lactams, the most important clinical defense against bacterial infections. However, due to the constant development of antibiotic-resistance mechanisms by bacteria, there is an ever-present need for new, more effective antimicrobial drugs. While enormous numbers of beta-lactam compounds have been tested for antibiotic activity in over 50 years of research, the success of a beta-lactam structure in terms of antibiotic activity remains unpredictable. Tipper and Strominger suggested long ago that beta-lactams inhibit DD-peptidases because they mimic the D-alanyl-D-alanine motif of the peptidoglycan substrate of these enzymes. They also predicted that beta-lactams having a peptidoglycan-mimetic side-chain might be better antibiotics than their non-specific counterparts, but decades of research have not provided any evidence for this. We have recently described two such novel beta-lactams. The first is a penicillin having the glycyl-L-alpha-amino-epsilon-pimelyl side-chain of Streptomyces strain R61 peptidoglycan, making it the "perfect penicillin" for this organism. The other is a cephalosporin with the same side-chain. Here, we describe the X-ray crystal structures of the perfect penicillin in non-covalent and covalent complexes with the Streptomyces R61 DD-peptidase. The structure of the non-covalent enzyme-inhibitor complex is the first such complex to be trapped crystallographically with a DD-peptidase. In addition, the covalent complex of the peptidyl-cephalosporin with the R61 DD-peptidase is described. Finally, two covalent complexes with the traditional beta-lactams benzylpenicillin and cephalosporin C were determined for comparison with the peptidyl beta-lactams. These structures, together with relevant kinetics data, support Tipper and Strominger's assertion that peptidoglycan-mimetic side-chains should improve beta-lactams as inhibitors of DD-peptidases.

Crystal structures of complexes between the R61 DD-peptidase and peptidoglycan-mimetic beta-lactams: a non-covalent complex with a "perfect penicillin".,Silvaggi NR, Josephine HR, Kuzin AP, Nagarajan R, Pratt RF, Kelly JA J Mol Biol. 2005 Jan 21;345(3):521-33. PMID:15581896<ref>PMID:15581896</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces sp. R61]]
[[Category: Josephine HR]]
[[Category: Kelly JA]]
[[Category: Pratt RF]]
[[Category: Silvaggi NR]]