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| | ==Crystal structure of a SMT fusion Peptidyl-prolyl cis-trans isomerase from Burkholderia pseudomallei complexed with CJ40== | | ==Crystal structure of a SMT fusion Peptidyl-prolyl cis-trans isomerase from Burkholderia pseudomallei complexed with CJ40== |
| - | <StructureSection load='4ggq' size='340' side='right' caption='[[4ggq]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='4ggq' size='340' side='right'caption='[[4ggq]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ggq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Burp1 Burp1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GGQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GGQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ggq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_pseudomallei_1710b Burkholderia pseudomallei 1710b] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GGQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GGQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=861:3-(3,4,5-TRIMETHOXYPHENYL)PROPYL+(2S)-1-(BENZYLSULFONYL)PIPERIDINE-2-CARBOXYLATE'>861</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 1.95Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2keo|2keo]], [[2ko7|2ko7]], [[2l2s|2l2s]], [[3vaw|3vaw]], [[3uqb|3uqb]], [[3uqa|3uqa]], [[4dz3|4dz3]], [[4dz2|4dz2]], [[3uf8|3uf8]], [[4fn2|4fn2]], [[4g50|4g50]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=861:3-(3,4,5-TRIMETHOXYPHENYL)PROPYL+(2S)-1-(BENZYLSULFONYL)PIPERIDINE-2-CARBOXYLATE'>861</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BURPS1710b_A0907, SMT3, YDR510W, D9719.15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=320372 BURP1])</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=4ggq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggq OCA], [https://pdbe.org/4ggq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ggq RCSB], [https://www.ebi.ac.uk/pdbsum/4ggq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ggq 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/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr>
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| - | <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=4ggq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ggq RCSB], [http://www.ebi.ac.uk/pdbsum/4ggq PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SMT3_YEAST SMT3_YEAST]] Not known; suppressor of MIF2 mutations. | + | [https://www.uniprot.org/uniprot/Q3JK38_BURP1 Q3JK38_BURP1] [https://www.uniprot.org/uniprot/SMT3_YEAST SMT3_YEAST] Not known; suppressor of MIF2 mutations. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Macrophage infectivity potentiators (Mips) are immunophilin proteins and essential virulence factors for a range of pathogenic organisms. We applied a structural biology approach to characterize a Mip from Burkholderia pseudomallei (BpML1), the causative agent of melioidosis. Crystal structure and nuclear magnetic resonance analyses of BpML1 in complex with known macrocyclics and other derivatives led to the identification of a key chemical scaffold. This scaffold possesses inhibitory potency for BpML1 without the immunosuppressive components of related macrocyclic agents. Biophysical characterization of a compound series with this scaffold allowed binding site specificity in solution and potency determinations for rank ordering the set. The best compounds in this series possessed a low-micromolar affinity for BpML1, bound at the site of enzymatic activity, and inhibited a panel of homologous Mip proteins from other pathogenic bacteria, without demonstrating toxicity in human macrophages. Importantly, the in vitro activity of BpML1 was reduced by these compounds, leading to decreased macrophage infectivity and intracellular growth of Burkholderia pseudomallei. These compounds offer the potential for activity against a new class of antimicrobial targets and present the utility of a structure-based approach for novel antimicrobial drug discovery.
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| - | A structural biology approach enables the development of antimicrobials targeting bacterial immunophilins.,Begley DW, Fox D 3rd, Jenner D, Juli C, Pierce PG, Abendroth J, Muruthi M, Safford K, Anderson V, Atkins K, Barnes SR, Moen SO, Raymond AC, Stacy R, Myler PJ, Staker BL, Harmer NJ, Norville IH, Holzgrabe U, Sarkar-Tyson M, Edwards TE, Lorimer DD Antimicrob Agents Chemother. 2014 Mar;58(3):1458-67. doi: 10.1128/AAC.01875-13., Epub 2013 Dec 23. PMID:24366729<ref>PMID:24366729</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Burp1]] | + | [[Category: Burkholderia pseudomallei 1710b]] |
| - | [[Category: Peptidylprolyl isomerase]] | + | [[Category: Large Structures]] |
| - | [[Category: Structural genomic]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Isomerase]]
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| - | [[Category: Protein binding]]
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| - | [[Category: Ssgcid]]
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