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| {{STRUCTURE_2qk8| PDB=2qk8 | SCENE= }} | | {{STRUCTURE_2qk8| PDB=2qk8 | SCENE= }} |
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| '''Crystal structure of the anthrax drug target, Bacillus anthracis dihydrofolate reductase'''
| | ===Crystal structure of the anthrax drug target, Bacillus anthracis dihydrofolate reductase=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17696333}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17696333 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17696333}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Pseudo-rossman fold]] | | [[Category: Pseudo-rossman fold]] |
| [[Category: Pteridine binding]] | | [[Category: Pteridine binding]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 15:06:22 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:32:43 2008'' |
