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| [[Image:1dyr.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1dyr| PDB=1dyr | SCENE= }} | | {{STRUCTURE_1dyr| PDB=1dyr | SCENE= }} |
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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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| ==Overview==
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| 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 line below this paragraph, {{ABSTRACT_PUBMED_7866743}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 7866743 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_7866743}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Stammers, D K.]] | | [[Category: Stammers, D K.]] |
| [[Category: Oxido-reductase]] | | [[Category: Oxido-reductase]] |
| ''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 Mon Jun 30 23:49:30 2008'' |