2vgk: Difference between revisions
New page: '''Unreleased structure''' The entry 2vgk is ON HOLD until Paper Publication Authors: Sauvage, E., kerff, F., Herman, R., Charlier, P. Description: Crystal structure of Actinomadura R3... |
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==Crystal structure of Actinomadura R39 DD-peptidase complexed with a peptidoglycan-mimetic cephalosporin== | |||
<StructureSection load='2vgk' size='340' side='right'caption='[[2vgk]], [[Resolution|resolution]] 2.25Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2vgk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Actinomadura_sp._R39 Actinomadura sp. R39]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VGK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VGK 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]] 2.25Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=REZ:(2R)-2-AMINO-7-{[(1R)-1-CARBOXYETHYL]AMINO}-7-OXOHEPTANOIC+ACID'>REZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2vgk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vgk OCA], [https://pdbe.org/2vgk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vgk RCSB], [https://www.ebi.ac.uk/pdbsum/2vgk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vgk ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DAC_ACTSP DAC_ACTSP] Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors. | |||
== 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/vg/2vgk_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=2vgk ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The X-ray crystal structures of covalent complexes of the Actinomadura R39 dd-peptidase and Escherichia coli penicillin-binding protein (PBP) 5 with beta-lactams bearing peptidoglycan-mimetic side chains have been determined. The structure of the hydrolysis product of an analogous peptide bound noncovalently to the former enzyme has also been obtained. The R39 DD-peptidase structures reveal the presence of a specific binding site for the D-alpha-aminopimelyl side chain, characteristic of the stem peptide of Actinomadura R39. This binding site features a hydrophobic cleft for the pimelyl methylene groups and strong hydrogen bonding to the polar terminus. Both of these active site elements are provided by amino acid side chains from two separate domains of the protein. In contrast, no clear electron density corresponding to the terminus of the peptidoglycan-mimetic side chains is present when these beta-lactams are covalently bound to PBP5. There is, therefore, no indication of a specific side-chain binding site in this enzyme. These results are in agreement with those from kinetics studies published earlier and support the general prediction made at the time of a direct correlation between kinetics and structural evidence. The essential high-molecular-mass PBPs have demonstrated, to date, no specific reactivity with peptidoglycan-mimetic peptide substrates and beta-lactam inhibitors and, thus, probably do not possess a specific substrate-binding site of the type demonstrated here with the R39 DD-peptidase. This striking deficiency may represent a sophisticated defense mechanism against low-molecular-mass substrate-analogue inhibitors/antibiotics; its discovery should focus new inhibitor design. | |||
Crystal structures of complexes of bacterial DD-peptidases with peptidoglycan-mimetic ligands: the substrate specificity puzzle.,Sauvage E, Powell AJ, Heilemann J, Josephine HR, Charlier P, Davies C, Pratt RF J Mol Biol. 2008 Aug 29;381(2):383-93. Epub 2008 Jun 10. PMID:18602645<ref>PMID:18602645</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2vgk" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]] | |||
*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Actinomadura sp. R39]] | |||
[[Category: Large Structures]] | |||
[[Category: Charlier P]] | |||
[[Category: Herman R]] | |||
[[Category: Sauvage E]] | |||
[[Category: Kerff F]] | |||
Latest revision as of 18:19, 13 December 2023
Crystal structure of Actinomadura R39 DD-peptidase complexed with a peptidoglycan-mimetic cephalosporinCrystal structure of Actinomadura R39 DD-peptidase complexed with a peptidoglycan-mimetic cephalosporin
Structural highlights
FunctionDAC_ACTSP Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe X-ray crystal structures of covalent complexes of the Actinomadura R39 dd-peptidase and Escherichia coli penicillin-binding protein (PBP) 5 with beta-lactams bearing peptidoglycan-mimetic side chains have been determined. The structure of the hydrolysis product of an analogous peptide bound noncovalently to the former enzyme has also been obtained. The R39 DD-peptidase structures reveal the presence of a specific binding site for the D-alpha-aminopimelyl side chain, characteristic of the stem peptide of Actinomadura R39. This binding site features a hydrophobic cleft for the pimelyl methylene groups and strong hydrogen bonding to the polar terminus. Both of these active site elements are provided by amino acid side chains from two separate domains of the protein. In contrast, no clear electron density corresponding to the terminus of the peptidoglycan-mimetic side chains is present when these beta-lactams are covalently bound to PBP5. There is, therefore, no indication of a specific side-chain binding site in this enzyme. These results are in agreement with those from kinetics studies published earlier and support the general prediction made at the time of a direct correlation between kinetics and structural evidence. The essential high-molecular-mass PBPs have demonstrated, to date, no specific reactivity with peptidoglycan-mimetic peptide substrates and beta-lactam inhibitors and, thus, probably do not possess a specific substrate-binding site of the type demonstrated here with the R39 DD-peptidase. This striking deficiency may represent a sophisticated defense mechanism against low-molecular-mass substrate-analogue inhibitors/antibiotics; its discovery should focus new inhibitor design. Crystal structures of complexes of bacterial DD-peptidases with peptidoglycan-mimetic ligands: the substrate specificity puzzle.,Sauvage E, Powell AJ, Heilemann J, Josephine HR, Charlier P, Davies C, Pratt RF J Mol Biol. 2008 Aug 29;381(2):383-93. Epub 2008 Jun 10. PMID:18602645[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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