1dyr

THE STRUCTURE OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE TO 1.9 ANGSTROMS RESOLUTIONTHE STRUCTURE OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE TO 1.9 ANGSTROMS RESOLUTION

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: , Gene: C-DNA P.CARINII DHFR (Pneumocystis carinii) Activity: Dihydrofolate reductase, with EC number 1.5.1.3 Resources: FirstGlance, OCA, RCSB, PDBsum 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

spinqualitylabelsall models 1dyr, resolution 1.86Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image