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1dyr
From Proteopedia
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'''THE STRUCTURE OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE TO 1.9 ANGSTROMS RESOLUTION''' | '''THE STRUCTURE OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE TO 1.9 ANGSTROMS RESOLUTION''' | ||
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[[Category: Delves, C J.]] | [[Category: Delves, C J.]] | ||
[[Category: Stammers, D K.]] | [[Category: Stammers, D K.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:26:44 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 11:26, 2 May 2008
THE STRUCTURE OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE TO 1.9 ANGSTROMS RESOLUTION
Overview
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.
About this Structure
1DYR is a Single protein structure of sequence from Pneumocystis carinii. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Fri May 2 14:26:44 2008
