1j3i
From Proteopedia
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| - | [[Image:1j3i.gif|left|200px]] | + | [[Image:1j3i.gif|left|200px]] |
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| - | '''Wild-type Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with WR99210, NADPH, and dUMP''' | + | {{Structure |
| + | |PDB= 1j3i |SIZE=350|CAPTION= <scene name='initialview01'>1j3i</scene>, resolution 2.33Å | ||
| + | |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</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene> and <scene name='pdbligand=UMP:2'-DEOXYURIDINE 5'-MONOPHOSPHATE'>UMP</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Wild-type Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with WR99210, NADPH, and dUMP''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1J3I is a [ | + | 1J3I is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J3I OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12704428 12704428] |
[[Category: Plasmodium falciparum]] | [[Category: Plasmodium falciparum]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: bifunctional]] | [[Category: bifunctional]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:58:27 2008'' |
Revision as of 09:58, 20 March 2008
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| , resolution 2.33Å | |||||||
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| Ligands: | , and | ||||||
| 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
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