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| | <StructureSection load='2qk8' size='340' side='right'caption='[[2qk8]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='2qk8' size='340' side='right'caption='[[2qk8]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qk8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis_(strain_sterne) Bacillus anthracis (strain sterne)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QK8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QK8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qk8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis_str._Sterne Bacillus anthracis str. Sterne]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QK8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QK8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</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]] 2.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dfrA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=260799 Bacillus anthracis (strain Sterne)])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </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=2qk8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qk8 OCA], [https://pdbe.org/2qk8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qk8 RCSB], [https://www.ebi.ac.uk/pdbsum/2qk8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qk8 ProSAT]</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=2qk8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qk8 OCA], [https://pdbe.org/2qk8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qk8 RCSB], [https://www.ebi.ac.uk/pdbsum/2qk8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qk8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/Q81R22_BACAN Q81R22_BACAN]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]
| + | [https://www.uniprot.org/uniprot/Q81R22_BACAN Q81R22_BACAN] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dihydrofolate reductase]] | + | [[Category: Bacillus anthracis str. Sterne]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bennett, B C]] | + | [[Category: Bennett BC]] |
| - | [[Category: Dealwis, C G]] | + | [[Category: Dealwis CG]] |
| - | [[Category: Lee, R E]] | + | [[Category: Lee RE]] |
| - | [[Category: Simmerman, R F]] | + | [[Category: Simmerman RF]] |
| - | [[Category: Xu, H]] | + | [[Category: Xu H]] |
| - | [[Category: Methotrexate]]
| + | |
| - | [[Category: Nucleotide phosphate binding]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Pseudo-rossman fold]]
| + | |
| - | [[Category: Pteridine binding]]
| + | |
| Structural highlights
Function
Q81R22_BACAN Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]
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
Spores of Bacillus anthracis are the infectious agent of anthrax. Current antibiotic treatments are limited due to resistance and patient age restrictions; thus, additional targets for therapeutic intervention are needed. One possible candidate is dihydrofolate reductase (DHFR), a biosynthetic enzyme necessary for anthrax pathogenicity. We determined the crystal structure of DHFR from B. anthracis (baDHFR) in complex with methotrexate (MTX; 1) at 2.4 Angstrom resolution. The structure reveals the crucial interactions required for MTX binding and a putative molecular basis for how baDHFR has natural resistance to trimethoprim (TMP; 2). The structure also allows insights for designing selective baDHFR inhibitors that will have weak affinities for the human enzyme. Additionally, we have found that 5-nitro-6-methylamino-isocytosine (MANIC; 3), which inhibits another B. anthracis folate synthesis enzyme, dihydropteroate synthase (DHPS), can also inhibit baDHFR. This provides a starting point for designing multi-target inhibitors that are less likely to induce drug resistance.
Crystal structure of the anthrax drug target, Bacillus anthracis dihydrofolate reductase.,Bennett BC, Xu H, Simmerman RF, Lee RE, Dealwis CG J Med Chem. 2007 Sep 6;50(18):4374-81. Epub 2007 Aug 14. PMID:17696333[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bennett BC, Xu H, Simmerman RF, Lee RE, Dealwis CG. Crystal structure of the anthrax drug target, Bacillus anthracis dihydrofolate reductase. J Med Chem. 2007 Sep 6;50(18):4374-81. Epub 2007 Aug 14. PMID:17696333 doi:10.1021/jm070319v
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