1dyr

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|PDB= 1dyr |SIZE=350|CAPTION= <scene name='initialview01'>1dyr</scene>, resolution 1.86&Aring;
|PDB= 1dyr |SIZE=350|CAPTION= <scene name='initialview01'>1dyr</scene>, resolution 1.86&Aring;
|SITE=
|SITE=
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|LIGAND= <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene> and <scene name='pdbligand=TOP:TRIMETHOPRIM'>TOP</scene>
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|LIGAND= <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=TOP:TRIMETHOPRIM'>TOP</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3]
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span>
|GENE= C-DNA P.CARINII DHFR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4754 Pneumocystis carinii])
|GENE= C-DNA P.CARINII DHFR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4754 Pneumocystis carinii])
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|DOMAIN=
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dyr OCA], [http://www.ebi.ac.uk/pdbsum/1dyr PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1dyr RCSB]</span>
}}
}}
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[[Category: Delves, C J.]]
[[Category: Delves, C J.]]
[[Category: Stammers, D K.]]
[[Category: Stammers, D K.]]
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[[Category: NDP]]
 
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[[Category: TOP]]
 
[[Category: oxido-reductase]]
[[Category: oxido-reductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:46:41 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:51:29 2008''

Revision as of 16:51, 30 March 2008


PDB ID 1dyr

Drag the structure with the mouse to rotate
, resolution 1.86Å
Ligands: ,
Gene: C-DNA P.CARINII DHFR (Pneumocystis carinii)
Activity: Dihydrofolate reductase, with EC number 1.5.1.3
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



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

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