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| | ==Crystal structure of an evolved putative penicillin-binding protein homolog, Rv2911, from Mycobacterium tuberculosis== | | ==Crystal structure of an evolved putative penicillin-binding protein homolog, Rv2911, from Mycobacterium tuberculosis== |
| - | <StructureSection load='4p0m' size='340' side='right' caption='[[4p0m]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4p0m' size='340' side='right'caption='[[4p0m]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4p0m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2bcf 2bcf]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P0M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P0M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4p0m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2bcf 2bcf]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P0M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P0M FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SEB:O-BENZYLSULFONYL-SERINE'>SEB</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SEB:O-BENZYLSULFONYL-SERINE'>SEB</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dacB, dacB2, MT2979, Rv2911 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=4p0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p0m OCA], [https://pdbe.org/4p0m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p0m RCSB], [https://www.ebi.ac.uk/pdbsum/4p0m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p0m ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4p0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p0m OCA], [http://pdbe.org/4p0m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p0m RCSB], [http://www.ebi.ac.uk/pdbsum/4p0m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p0m ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q7D6F2_MYCTO Q7D6F2_MYCTO] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Serine-type D-Ala-D-Ala carboxypeptidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Bursey, E]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Hung, L W]] | + | [[Category: Bursey E]] |
| - | [[Category: Krieger, I]] | + | [[Category: Hung L-W]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Krieger I]] |
| - | [[Category: Terwilliger, T C]] | + | [[Category: Terwilliger TC]] |
| - | [[Category: Yu, M]] | + | [[Category: Yu M]] |
| - | [[Category: Dd-2 carboxypeptidase]]
| + | |
| - | [[Category: Directed evolution]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Penicillin-binding protein]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Tbsgc]]
| + | |
| Structural highlights
Function
Q7D6F2_MYCTO
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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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