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| | <StructureSection load='1ikg' size='340' side='right'caption='[[1ikg]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='1ikg' size='340' side='right'caption='[[1ikg]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1ikg]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_sp. Streptomyces sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IKG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1IKG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ikg]] 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=1IKG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IKG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=REX:GLYCYL-L-ALPHA-AMINO-EPSILON-PIMELYL-D-ALANYL-D-ALANINE'>REX</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hvb|1hvb]], [[3pte|3pte]], [[1iki|1iki]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=REX:GLYCYL-L-ALPHA-AMINO-EPSILON-PIMELYL-D-ALANYL-D-ALANINE'>REX</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Serine-type_D-Ala-D-Ala_carboxypeptidase Serine-type D-Ala-D-Ala carboxypeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.16.4 3.4.16.4] </span></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=1ikg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ikg OCA], [https://pdbe.org/1ikg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ikg RCSB], [https://www.ebi.ac.uk/pdbsum/1ikg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ikg ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ikg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ikg OCA], [http://pdbe.org/1ikg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ikg RCSB], [http://www.ebi.ac.uk/pdbsum/1ikg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ikg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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). | + | [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 == | | == 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/ik/1ikg_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ik/1ikg_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <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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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Serine-type D-Ala-D-Ala carboxypeptidase]]
| + | [[Category: Streptomyces sp. R61]] |
| - | [[Category: Streptomyces sp]] | + | [[Category: Anderson JW]] |
| - | [[Category: Anderson, J W]] | + | [[Category: Kelly JA]] |
| - | [[Category: Kelly, J A]] | + | [[Category: Knox JR]] |
| - | [[Category: Knox, J R]] | + | [[Category: Mcdonough MA]] |
| - | [[Category: Mcdonough, M A]] | + | [[Category: Pratt RF]] |
| - | [[Category: Pratt, R F]] | + | [[Category: Silvaggi NR]] |
| - | [[Category: Silvaggi, N R]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Michaelis complex]]
| + | |
| - | [[Category: Penicillin binding protein]]
| + | |
| - | [[Category: Peptidoglycan]]
| + | |
| Structural highlights
Function
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
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Penicillin-binding proteins (PBPs), the target enzymes of beta-lactam antibiotics such as penicillins and cephalosporins, catalyze the final peptidoglycan cross-linking step of bacterial cell-wall biosynthesis. beta-Lactams inhibit this reaction because they mimic the D-alanyl-D-alanine peptide precursors of cell-wall structure. Prior crystallographic studies have described the site of beta-lactam binding and inhibition, but they have failed to show the binding of D-Ala-D-Ala substrates. We present here the first high-resolution crystallographic structures of a PBP, D-Ala-D-Ala-peptidase of Streptomyces sp. strain R61, non-covalently complexed with a highly specific fragment (glycyl-L-alpha-amino-epsilon-pimelyl-D-Ala-D-Ala) of the cell-wall precursor in both enzyme-substrate and enzyme-product forms. The 1.9A resolution structure of the enzyme-substrate Henri-Michaelis complex was achieved by using inactivated enzyme, which was formed by cross-linking two catalytically important residues Tyr159 and Lys65. The second structure at 1.25A resolution of the uncross-linked, active form of the DD-peptidase shows the non-covalent binding of the two products of the carboxypeptidase reaction. The well-defined substrate-binding site in the two crystallographic structures shows a subsite that is complementary to a portion of the natural cell-wall substrate that varies among bacterial species. In addition, the structures show the displacement of 11 water molecules from the active site, the location of residues responsible for substrate binding, and clearly demonstrate the necessity of Lys65 and or Tyr159 for the acylation step with the donor peptide. Comparison of the complexed structures described here with the structures of other known PBPs suggests the design of species-targeted antibiotics as a counter-strategy towards beta-lactamase-elicited bacterial resistance.
Structures of two kinetic intermediates reveal species specificity of penicillin-binding proteins.,McDonough MA, Anderson JW, Silvaggi NR, Pratt RF, Knox JR, Kelly JA J Mol Biol. 2002 Sep 6;322(1):111-22. PMID:12215418[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ McDonough MA, Anderson JW, Silvaggi NR, Pratt RF, Knox JR, Kelly JA. Structures of two kinetic intermediates reveal species specificity of penicillin-binding proteins. J Mol Biol. 2002 Sep 6;322(1):111-22. PMID:12215418
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