1pwc: Difference between revisions
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==penicilloyl acyl enzyme complex of the Streptomyces R61 DD-peptidase with penicillin G== | |||
<StructureSection load='1pwc' size='340' side='right'caption='[[1pwc]], [[Resolution|resolution]] 1.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1pwc]] 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=1PWC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PWC 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]] 1.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PNM:OPEN+FORM+-+PENICILLIN+G'>PNM</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=1pwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pwc OCA], [https://pdbe.org/1pwc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pwc RCSB], [https://www.ebi.ac.uk/pdbsum/1pwc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pwc 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/1pwc_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1pwc ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1pwc" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Carboxypeptidase|Carboxypeptidase]] | *[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]] | ||
== References == | |||
<references/> | |||
== | __TOC__ | ||
< | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Streptomyces sp.]] | [[Category: Streptomyces sp. R61]] | ||
[[Category: Josephine | [[Category: Josephine HR]] | ||
[[Category: Kelly | [[Category: Kelly JA]] | ||
[[Category: Pratt | [[Category: Pratt RF]] | ||
[[Category: Silvaggi | [[Category: Silvaggi NR]] | ||
