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| | <StructureSection load='4ppr' size='340' side='right'caption='[[4ppr]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='4ppr' size='340' side='right'caption='[[4ppr]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ppr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PPR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PPR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ppr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PPR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PPR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MER:(4R,5S)-3-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-5-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-4-METHYL-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>MER</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MER:(4R,5S)-3-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-5-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-4-METHYL-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>MER</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4p0m|4p0m]]</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=4ppr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppr OCA], [https://pdbe.org/4ppr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ppr RCSB], [https://www.ebi.ac.uk/pdbsum/4ppr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppr ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rv3330, RVBD_3330 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=4ppr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppr OCA], [http://pdbe.org/4ppr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ppr RCSB], [http://www.ebi.ac.uk/pdbsum/4ppr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DACB1_MYCTU DACB1_MYCTU] Probably cleaves the terminal D-Ala-D-Ala dipeptide of the peptidoglycan stem peptide (Probable). Shows weak D,D-carboxypeptidase activity in vitro (PubMed:22906310). Acts on the synthetic penta-peptide substrate Penta-DAP (L-Ala-gamma-D-Gln-DAP-D-Ala-D-Ala) (PubMed:22906310). The catalytic domain binds weakly to peptidoglycan in vitro (PubMed:25551456).<ref>PMID:22906310</ref> <ref>PMID:25551456</ref> <ref>PMID:22906310</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4ppr" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4ppr" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Alber, T]] | + | [[Category: Alber T]] |
| - | [[Category: Huizar, J P]] | + | [[Category: Huizar JP]] |
| - | [[Category: Mavrici, D]] | + | [[Category: Mavrici D]] |
| - | [[Category: Prigozhin, D M]] | + | [[Category: Prigozhin DM]] |
| - | [[Category: Structural genomic]]
| + | |
| - | [[Category: D-peptidase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: National institute of allergy and infectious disease]]
| + | |
| - | [[Category: Niaid]]
| + | |
| - | [[Category: Penicillin-binding protein]]
| + | |
| - | [[Category: Peptidoglycan d]]
| + | |
| - | [[Category: Tbsgc]]
| + | |
| Structural highlights
Function
DACB1_MYCTU Probably cleaves the terminal D-Ala-D-Ala dipeptide of the peptidoglycan stem peptide (Probable). Shows weak D,D-carboxypeptidase activity in vitro (PubMed:22906310). Acts on the synthetic penta-peptide substrate Penta-DAP (L-Ala-gamma-D-Gln-DAP-D-Ala-D-Ala) (PubMed:22906310). The catalytic domain binds weakly to peptidoglycan in vitro (PubMed:25551456).[1] [2] [3]
Publication Abstract from PubMed
Beta-lactam antibiotics target penicillin-binding proteins including several enzyme classes essential for bacterial cell-wall homeostasis. To better understand the functional and inhibitor-binding specificities of penicillin-binding proteins from the pathogen, Mycobacterium tuberculosis, we carried out structural and phylogenetic analysis of two predicted D,D-carboxypeptidases, Rv2911 and Rv3330. Optimization of Rv2911 for crystallization using directed evolution and the GFP folding reporter method yielded a soluble quadruple mutant. Structures of optimized Rv2911 bound to phenylmethylsulfonyl fluoride and Rv3330 bound to meropenem show that, in contrast to the nonspecific inhibitor, meropenem forms an extended interaction with the enzyme along a conserved surface. Phylogenetic analysis shows that Rv2911 and Rv3330 belong to different clades that emerged in Actinobacteria and are not represented in model organisms such as Escherichia coli and Bacillus subtilis. Clade-specific adaptations allow these enzymes to fulfill distinct physiological roles despite strict conservation of core catalytic residues. The characteristic differences include potential protein-protein interaction surfaces and specificity-determining residues surrounding the catalytic site. Overall, these structural insights lay the groundwork to develop improved beta-lactam therapeutics for tuberculosis.
Subfamily-Specific Adaptations in the Structures of Two Penicillin-Binding Proteins from Mycobacterium tuberculosis.,Prigozhin DM, Krieger IV, Huizar JP, Mavrici D, Waldo GS, Hung LW, Sacchettini JC, Terwilliger TC, Alber T PLoS One. 2014 Dec 31;9(12):e116249. doi: 10.1371/journal.pone.0116249., eCollection 2014. PMID:25551456[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kumar P, Arora K, Lloyd JR, Lee IY, Nair V, Fischer E, Boshoff HI, Barry CE 3rd. Meropenem inhibits D,D-carboxypeptidase activity in Mycobacterium tuberculosis. Mol Microbiol. 2012 Oct;86(2):367-81. PMID:22906310 doi:10.1111/j.1365-2958.2012.08199.x
- ↑ Prigozhin DM, Krieger IV, Huizar JP, Mavrici D, Waldo GS, Hung LW, Sacchettini JC, Terwilliger TC, Alber T. Subfamily-Specific Adaptations in the Structures of Two Penicillin-Binding Proteins from Mycobacterium tuberculosis. PLoS One. 2014 Dec 31;9(12):e116249. doi: 10.1371/journal.pone.0116249., eCollection 2014. PMID:25551456 doi:http://dx.doi.org/10.1371/journal.pone.0116249
- ↑ Kumar P, Arora K, Lloyd JR, Lee IY, Nair V, Fischer E, Boshoff HI, Barry CE 3rd. Meropenem inhibits D,D-carboxypeptidase activity in Mycobacterium tuberculosis. Mol Microbiol. 2012 Oct;86(2):367-81. PMID:22906310 doi:10.1111/j.1365-2958.2012.08199.x
- ↑ Prigozhin DM, Krieger IV, Huizar JP, Mavrici D, Waldo GS, Hung LW, Sacchettini JC, Terwilliger TC, Alber T. Subfamily-Specific Adaptations in the Structures of Two Penicillin-Binding Proteins from Mycobacterium tuberculosis. PLoS One. 2014 Dec 31;9(12):e116249. doi: 10.1371/journal.pone.0116249., eCollection 2014. PMID:25551456 doi:http://dx.doi.org/10.1371/journal.pone.0116249
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