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New page: left|200px<br /><applet load="1dyr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dyr, resolution 1.86Å" /> '''THE STRUCTURE OF PNE...
 
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[[Image:1dyr.gif|left|200px]]<br /><applet load="1dyr" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1dyr, resolution 1.86&Aring;" />
'''THE STRUCTURE OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE TO 1.9 ANGSTROMS RESOLUTION'''<br />


==Overview==
==THE STRUCTURE OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE TO 1.9 ANGSTROMS RESOLUTION==
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.
<StructureSection load='1dyr' size='340' side='right'caption='[[1dyr]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1dyr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pneumocystis_carinii Pneumocystis carinii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DYR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.86&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=TOP:TRIMETHOPRIM'>TOP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1dyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dyr OCA], [https://pdbe.org/1dyr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dyr RCSB], [https://www.ebi.ac.uk/pdbsum/1dyr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dyr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DYR_PNECA 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 ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dy/1dyr_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1dyr ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1DYR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pneumocystis_carinii Pneumocystis carinii] with NDP and TOP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1DYR OCA].
*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7866743 7866743]
[[Category: Large Structures]]
[[Category: Dihydrofolate reductase]]
[[Category: Pneumocystis carinii]]
[[Category: Pneumocystis carinii]]
[[Category: Single protein]]
[[Category: Achari A]]
[[Category: Achari, A.]]
[[Category: Ballantine SP]]
[[Category: Ballantine, S.P.]]
[[Category: Bryant PK]]
[[Category: Bryant, P.K.]]
[[Category: Champness JN]]
[[Category: Champness, J.N.]]
[[Category: Delves CJ]]
[[Category: Delves, C.J.]]
[[Category: Stammers DK]]
[[Category: Stammers, D.K.]]
[[Category: NDP]]
[[Category: TOP]]
[[Category: oxido-reductase]]
 
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Retrieved from "https://proteopedia.org/1dyr"