3fl8

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[[Image:3fl8.png|left|200px]]
 
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{{STRUCTURE_3fl8| PDB=3fl8 | SCENE= }}
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==Crystal structure of B. anthracis dihydrofolate reductase (DHFR) with RAB1, a TMP-dihydrophthalazine derivative==
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<StructureSection load='3fl8' size='340' side='right'caption='[[3fl8]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3fl8]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FL8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FL8 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2881&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=RAR:5-(3,4-DIMETHOXY-5-{(1E)-3-OXO-3-[(1S)-1-PROPYLPHTHALAZIN-2(1H)-YL]PROP-1-EN-1-YL}BENZYL)PYRIMIDINE-2,4-DIAMINE'>RAR</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3fl8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fl8 OCA], [https://pdbe.org/3fl8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fl8 RCSB], [https://www.ebi.ac.uk/pdbsum/3fl8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fl8 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q81R22_BACAN Q81R22_BACAN] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fl/3fl8_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=3fl8 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Bacillus anthracis possesses an innate resistance to the antibiotic trimethoprim due to poor binding to dihydrofolate reductase (DHFR); currently, there are no commercial antibacterials that target this enzyme in B. anthracis. We have previously reported a series of dihydrophthalazine-based trimethoprim derivatives that are inhibitors for this target. In the present work, we have synthesized one compound (RAB1) displaying favorable 50% inhibitory concentration (54 nM) and MIC (&lt; or =12.8 microg/ml) values. RAB1 was cocrystallized with the B. anthracis DHFR in the space group P2(1)2(1)2(1), and X-ray diffraction data were collected to a 2.3-A resolution. Binding of RAB1 causes a conformational change of the side chain of Arg58 and Met37 to accommodate the dihydrophthalazine moiety. Unlike the natural substrate or trimethoprim, the dihydrophthalazine group provides a large hydrophobic anchor that embeds within the DHFR active site and accounts for its selective inhibitory activity against B. anthracis.
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===Crystal structure of B. anthracis dihydrofolate reductase (DHFR) with RAB1, a TMP-dihydrophthalazine derivative===
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Crystal structure of Bacillus anthracis dihydrofolate reductase with the dihydrophthalazine-based trimethoprim derivative RAB1 provides a structural explanation of potency and selectivity.,Bourne CR, Bunce RA, Bourne PC, Berlin KD, Barrow EW, Barrow WW Antimicrob Agents Chemother. 2009 Jul;53(7):3065-73. Epub 2009 Apr 13. PMID:19364848<ref>PMID:19364848</ref>
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{{ABSTRACT_PUBMED_19364848}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 3fl8" style="background-color:#fffaf0;"></div>
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[[3fl8]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FL8 OCA].
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==See Also==
==See Also==
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*[[Dihydrofolate reductase|Dihydrofolate reductase]]
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*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019364848</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Bacillus anthracis]]
[[Category: Bacillus anthracis]]
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[[Category: Dihydrofolate reductase]]
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[[Category: Large Structures]]
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[[Category: Barrow, W W.]]
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[[Category: Barrow WW]]
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[[Category: Bourne, C R.]]
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[[Category: Bourne CR]]
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[[Category: Dihydrophthalazine]]
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[[Category: Oxidoreductase]]
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[[Category: Pyrimidine]]
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Current revision

Crystal structure of B. anthracis dihydrofolate reductase (DHFR) with RAB1, a TMP-dihydrophthalazine derivative

PDB ID 3fl8

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