1j3i

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[[Image:1j3i.gif|left|200px]]
[[Image:1j3i.gif|left|200px]]
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{{Structure
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|PDB= 1j3i |SIZE=350|CAPTION= <scene name='initialview01'>1j3i</scene>, resolution 2.33&Aring;
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The line below this paragraph, containing "STRUCTURE_1j3i", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=UMP:2&#39;-DEOXYURIDINE+5&#39;-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>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY=
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or leave the SCENE parameter empty for the default display.
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|GENE=
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|DOMAIN=
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{{STRUCTURE_1j3i| PDB=1j3i | SCENE= }}
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|RELATEDENTRY=[[1j3j|1J3J]], [[1j3k|1J3K]]
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|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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}}
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'''Wild-type Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with WR99210, NADPH, and dUMP'''
'''Wild-type Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with WR99210, NADPH, and dUMP'''
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[[Category: Yuthavong, Y.]]
[[Category: Yuthavong, Y.]]
[[Category: Yuvaniyama, J.]]
[[Category: Yuvaniyama, J.]]
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[[Category: bifunctional]]
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[[Category: Bifunctional]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:45:36 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:28:20 2008''
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Revision as of 17:45, 2 May 2008

Image:1j3i.gif

Template:STRUCTURE 1j3i

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 Fri May 2 20:45:36 2008

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