1j3i
From Proteopedia
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|PDB= 1j3i |SIZE=350|CAPTION= <scene name='initialview01'>1j3i</scene>, resolution 2.33Å | |PDB= 1j3i |SIZE=350|CAPTION= <scene name='initialview01'>1j3i</scene>, resolution 2.33Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=WRA:6,6-DIMETHYL-1-[3-(2,4,5-TRICHLOROPHENOXY)PROPOXY]-1,6-DIHYDRO-1,3,5-TRIAZINE-2,4-DIAMINE'>WRA | + | |LIGAND= <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=UMP:2'-DEOXYURIDINE+5'-MONOPHOSPHATE'>UMP</scene>, <scene name='pdbligand=WRA:6,6-DIMETHYL-1-[3-(2,4,5-TRICHLOROPHENOXY)PROPOXY]-1,6-DIHYDRO-1,3,5-TRIAZINE-2,4-DIAMINE'>WRA</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1j3j|1J3J]], [[1j3k|1J3K]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1j3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j3i OCA], [http://www.ebi.ac.uk/pdbsum/1j3i PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1j3i RCSB]</span> | ||
}} | }} | ||
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[[Category: Yuthavong, Y.]] | [[Category: Yuthavong, Y.]] | ||
[[Category: Yuvaniyama, J.]] | [[Category: Yuvaniyama, J.]] | ||
| - | [[Category: NDP]] | ||
| - | [[Category: UMP]] | ||
| - | [[Category: WRA]] | ||
[[Category: bifunctional]] | [[Category: bifunctional]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:28:20 2008'' |
Revision as of 18:28, 30 March 2008
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| , resolution 2.33Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Related: | 1J3J, 1J3K
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Wild-type Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with WR99210, NADPH, and dUMP
Overview
Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) is an important target of antimalarial drugs. The efficacy of this class of DHFR-inhibitor drugs is now compromised because of mutations that prevent drug binding yet retain enzyme activity. The crystal structures of PfDHFR-TS from the wild type (TM4/8.2) and the quadruple drug-resistant mutant (V1/S) strains, in complex with a potent inhibitor WR99210, as well as the resistant double mutant (K1 CB1) with the antimalarial pyrimethamine, reveal features for overcoming resistance. In contrast to pyrimethamine, the flexible side chain of WR99210 can adopt a conformation that fits well in the active site, thereby contributing to binding. The single-chain bifunctional PfDHFR-TS has a helical insert between the DHFR and TS domains that is involved in dimerization and domain organization. Moreover, positively charged grooves on the surface of the dimer suggest a function in channeling of substrate from TS to DHFR active sites. These features provide possible approaches for the design of new drugs to overcome antifolate resistance.
About this Structure
1J3I is a Protein complex structure of sequences from Plasmodium falciparum. Full crystallographic information is available from OCA.
Reference
Insights into antifolate resistance from malarial DHFR-TS structures., Yuvaniyama J, Chitnumsub P, Kamchonwongpaisan S, Vanichtanankul J, Sirawaraporn W, Taylor P, Walkinshaw MD, Yuthavong Y, Nat Struct Biol. 2003 May;10(5):357-65. PMID:12704428
Page seeded by OCA on Sun Mar 30 21:28:20 2008
