2qk8
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene> | |LIGAND= <scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene> | ||
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span> |
|GENE= dfrA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 Bacillus anthracis]) | |GENE= dfrA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 Bacillus anthracis]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qk8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qk8 OCA], [http://www.ebi.ac.uk/pdbsum/2qk8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qk8 RCSB]</span> | ||
}} | }} | ||
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[[Category: Simmerman, R F.]] | [[Category: Simmerman, R F.]] | ||
[[Category: Xu, H.]] | [[Category: Xu, H.]] | ||
| - | [[Category: MTX]] | ||
[[Category: methotrexate]] | [[Category: methotrexate]] | ||
[[Category: nucleotide phosphate binding]] | [[Category: nucleotide phosphate binding]] | ||
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[[Category: pteridine binding]] | [[Category: pteridine binding]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:50:12 2008'' |
Revision as of 01:50, 31 March 2008
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| , resolution 2.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | dfrA (Bacillus anthracis) | ||||||
| Activity: | Dihydrofolate reductase, with EC number 1.5.1.3 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the anthrax drug target, Bacillus anthracis dihydrofolate reductase
Overview
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.
About this Structure
2QK8 is a Single protein structure of sequence from Bacillus anthracis. Full crystallographic information is available from OCA.
Reference
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
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