2xd5
From Proteopedia
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<StructureSection load='2xd5' size='340' side='right'caption='[[2xd5]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='2xd5' size='340' side='right'caption='[[2xd5]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2xd5]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[2xd5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_R6 Streptococcus pneumoniae R6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XD5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XD5 FirstGlance]. <br> |
| - | </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=S2D:N-BENZOYL-D-ALANINE'>S2D</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</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=S2D:N-BENZOYL-D-ALANINE'>S2D</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'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xd5 OCA], [https://pdbe.org/2xd5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xd5 RCSB], [https://www.ebi.ac.uk/pdbsum/2xd5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xd5 ProSAT]</span></td></tr> |
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q7CRA4_STRR6 Q7CRA4_STRR6] | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xd/2xd5_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xd/2xd5_consurf.spt"</scriptWhenChecked> | ||
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
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Class A penicillin-binding proteins (PBPs) catalyze the last two steps in the biosynthesis of peptidoglycan, a key component of the bacterial cell wall. Both reactions, glycosyl transfer (polymerization of glycan chains) and transpeptidation (cross-linking of stem peptides), are essential for peptidoglycan stability and for the cell division process, but remain poorly understood. The PBP-catalyzed transpeptidation reaction is the target of beta-lactam antibiotics, but their vast employment worldwide has prompted the appearance of highly resistant strains, thus requiring concerted efforts towards an understanding of the transpeptidation reaction with the goal of developing better antibacterials. This goal, however, has been elusive, since PBP substrates are rapidly deacylated. In this work, we provide a structural snapshot of a "trapped" covalent intermediate of the reaction between a class A PBP with a pseudo-substrate, N-benzoyl-D-alanylmercaptoacetic acid thioester, which partly mimics the stem peptides contained within the natural, membrane-associated substrate, lipid II. The structure reveals that the D-alanyl moiety of the covalent intermediate (N-benzoyl-d-alanine) is stabilized in the cleft by a network of hydrogen bonds that place the carbonyl group in close proximity to the oxyanion hole, thus mimicking the spatial arrangement of beta-lactam antibiotics within the PBP active site. This arrangement allows the target bond to be in optimal position for attack by the acceptor peptide and is similar to the structural disposition of beta-lactam antibiotics with PBP clefts. This information yields a better understanding of PBP catalysis and could provide key insights into the design of novel PBP inhibitors. | Class A penicillin-binding proteins (PBPs) catalyze the last two steps in the biosynthesis of peptidoglycan, a key component of the bacterial cell wall. Both reactions, glycosyl transfer (polymerization of glycan chains) and transpeptidation (cross-linking of stem peptides), are essential for peptidoglycan stability and for the cell division process, but remain poorly understood. The PBP-catalyzed transpeptidation reaction is the target of beta-lactam antibiotics, but their vast employment worldwide has prompted the appearance of highly resistant strains, thus requiring concerted efforts towards an understanding of the transpeptidation reaction with the goal of developing better antibacterials. This goal, however, has been elusive, since PBP substrates are rapidly deacylated. In this work, we provide a structural snapshot of a "trapped" covalent intermediate of the reaction between a class A PBP with a pseudo-substrate, N-benzoyl-D-alanylmercaptoacetic acid thioester, which partly mimics the stem peptides contained within the natural, membrane-associated substrate, lipid II. The structure reveals that the D-alanyl moiety of the covalent intermediate (N-benzoyl-d-alanine) is stabilized in the cleft by a network of hydrogen bonds that place the carbonyl group in close proximity to the oxyanion hole, thus mimicking the spatial arrangement of beta-lactam antibiotics within the PBP active site. This arrangement allows the target bond to be in optimal position for attack by the acceptor peptide and is similar to the structural disposition of beta-lactam antibiotics with PBP clefts. This information yields a better understanding of PBP catalysis and could provide key insights into the design of novel PBP inhibitors. | ||
| - | Trapping of an acyl-enzyme intermediate in a penicillin-binding protein (PBP)-catalyzed reaction.,Macheboeuf P, Lemaire D, Teller N, Martins Ados S, Luxen A, Dideberg O, Jamin M, Dessen A J Mol Biol. 2008 Feb 15;376(2):405-13. Epub 2007 Nov 1. PMID: | + | Trapping of an acyl-enzyme intermediate in a penicillin-binding protein (PBP)-catalyzed reaction.,Macheboeuf P, Lemaire D, Teller N, Martins Ados S, Luxen A, Dideberg O, Jamin M, Dessen A J Mol Biol. 2008 Feb 15;376(2):405-13. Epub 2007 Nov 1. PMID:018155726<ref>PMID:018155726</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Streptococcus pneumoniae R6]] |
| - | [[Category: Dessen | + | [[Category: Dessen A]] |
| - | [[Category: Dideberg | + | [[Category: Dideberg O]] |
| - | [[Category: Jamin | + | [[Category: Jamin M]] |
| - | [[Category: Lemaire | + | [[Category: Lemaire D]] |
| - | [[Category: Macheboeuf | + | [[Category: Macheboeuf P]] |
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Current revision
Structural insights into the catalytic mechanism and the role of Streptococcus pneumoniae PBP1b
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