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<StructureSection load='1m7a' size='340' side='right'caption='[[1m7a]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
<StructureSection load='1m7a' size='340' side='right'caption='[[1m7a]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1m7a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_11006_[[candida_stellatoidea]] Atcc 11006 [[candida stellatoidea]]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M7A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1M7A FirstGlance]. <br>
<table><tr><td colspan='2'>[[1m7a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_albicans Candida albicans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M7A FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MQU:7-[2-METHOXY-1-(METHOXYMETHYL)ETHYL]-7H-PYRROLO[3,2-F]+QUINAZOLINE-1,3-DIAMINE'>MQU</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.76&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ai9|1ai9]], [[1aoe|1aoe]], [[1ia1|1ia1]], [[1ia2|1ia2]], [[1ai3|1ai3]], [[1ai4|1ai4]], [[1m78|1m78]], [[1m79|1m79]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MQU:7-[2-METHOXY-1-(METHOXYMETHYL)ETHYL]-7H-PYRROLO[3,2-F]+QUINAZOLINE-1,3-DIAMINE'>MQU</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DFR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5476 ATCC 11006 [[Candida stellatoidea]]])</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=1m7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m7a OCA], [https://pdbe.org/1m7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m7a RCSB], [https://www.ebi.ac.uk/pdbsum/1m7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m7a ProSAT]</span></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1m7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m7a OCA], [http://pdbe.org/1m7a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1m7a RCSB], [http://www.ebi.ac.uk/pdbsum/1m7a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1m7a ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/DYR_CANAX DYR_CANAX]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.  
[https://www.uniprot.org/uniprot/DYR_CANAX DYR_CANAX] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=1m7a ConSurf].
</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=1m7a ConSurf].
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== Publication Abstract from PubMed ==
The recent rise in systemic fungal infections has created a need for the development of new antifungal agents. As part of an effort to provide therapeutically effective inhibitors of fungal dihydrofolate reductase (DHFR), we have cloned, expressed, purified, crystallized, and determined the three-dimensional structure of Candida albicans DHFR. The 192-residue enzyme, which was expressed in Escherichia coli and purified by methotrexate affinity and cation exchange chromatography, was 27% identical to human DHFR. Crystals of C. albicans DHFR were grown as the holoenzyme complex and as a ternary complex containing a pyrroloquinazoline inhibitor. Both complexes crystallized with two molecules in the asymmetric unit in space group P21. The final structures had R-factors of 0.199 at 1.85-A resolution and 0.155 at 1.60-A resolution, respectively. The enzyme fold was similar to that of bacterial and vertebrate DHFR, and the binding of a nonselective diaminopyrroloquinazoline inhibitor and the interactions of NADPH with protein were typical of ligand binding to other DHFRs. However, the width of the active site cleft of C. albicans DHFR was significantly larger than that of the human enzyme, providing a basis for the design of potentially selective inhibitors.
X-ray crystallographic studies of Candida albicans dihydrofolate reductase. High resolution structures of the holoenzyme and an inhibited ternary complex.,Whitlow M, Howard AJ, Stewart D, Hardman KD, Kuyper LF, Baccanari DP, Fling ME, Tansik RL J Biol Chem. 1997 Nov 28;272(48):30289-98. PMID:9374515<ref>PMID:9374515</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1m7a" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Dihydrofolate reductase]]
[[Category: Candida albicans]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Howard, A J]]
[[Category: Howard AJ]]
[[Category: Kuyper, L F]]
[[Category: Kuyper LF]]
[[Category: Whitlow, M]]
[[Category: Whitlow M]]
[[Category: Antifungal target]]
[[Category: Oxidoreductase]]
[[Category: Reductase]]

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