1dyr | pdb_00001dyr

THE STRUCTURE OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE TO 1.9 ANGSTROMS RESOLUTION

spinqualitylabelsall models 1dyr, resolution 1.86Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1dyr is a 1 chain structure with sequence from Pneumocystis carinii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NDP, TOP Gene: C-DNA P.CARINII DHFR (Pneumocystis carinii) Activity: Dihydrofolate reductase, with EC number 1.5.1.3 Resources: FirstGlance, OCA, RCSB, PDBsum Function [DYR_PNECA] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed BACKGROUND: The fungal pathogen Pneumocystis carinii causes a pneumonia which is an opportunistic infection of AIDS patients. Current therapy includes the dihydrofolate reductase (DHFR) inhibitor trimethoprim which is selective but only a relatively weak inhibitor of the enzyme for P. carinii. Determination of the three-dimensional structure of the enzyme should form the basis for design of more potent and selective therapeutic agents for treatment of the disease. RESULTS: The structure of P. carinii DHFR in complex with reduced nicotinamide adenine dinucleotide phosphate and trimethoprim has accordingly been solved by X-ray crystallography. The structure of the ternary complex has been refined at 1.86 A resolution (R = 0.181). A similar ternary complex with piritrexim (which is a tighter binding, but less selective inhibitor) has also been solved, as has the binary complex holoenzyme, both at 2.5 A resolution. CONCLUSIONS: These structures show how two drugs interact with a fungal DHFR. A comparison of the three-dimensional structure of this relatively large DHFR with bacterial or mammalian enzyme-inhibitor complexes determined previously highlights some additional secondary structure elements in this particular enzyme species. These comparisons provide further insight into the principles governing DHFR-inhibitor interaction, in which the volume of the active site appears to determine the strength of inhibitor binding. The structure of Pneumocystis carinii dihydrofolate reductase to 1.9 A resolution.,Champness JN, Achari A, Ballantine SP, Bryant PK, Delves CJ, Stammers DK Structure. 1994 Oct 15;2(10):915-24. PMID:7866743 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dihydrofolate reductase

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