3fl9: Difference between revisions

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-[[Image:3fl9.png|left|200px]]
-{{STRUCTURE_3fl9|  PDB=3fl9  |  SCENE=  }}
+==Crystal structure of B. anthracis dihydrofolate reductase (DHFR) with trimethoprim==
+<StructureSection load='3fl9' size='340' side='right'caption='[[3fl9]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3fl9]] 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=3FL9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FL9 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]] 2.4&#8491;</td></tr>
+<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=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=3fl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fl9 OCA], [https://pdbe.org/3fl9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fl9 RCSB], [https://www.ebi.ac.uk/pdbsum/3fl9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fl9 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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]
+== 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/fl/3fl9_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=3fl9 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-===Crystal structure of B. anthracis dihydrofolate reductase (DHFR) with trimethoprim===
+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>
-{{ABSTRACT_PUBMED_19364848}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 3fl9" style="background-color:#fffaf0;"></div>
-[[3fl9]] 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=3FL9 OCA].
 ==See Also==
-*[[Dihydrofolate reductase|Dihydrofolate reductase]]
+*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:019364848</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Bacillus anthracis]]
-[[Category: Dihydrofolate reductase]]
+[[Category: Large Structures]]
-[[Category: Barrow, W W.]]
+[[Category: Barrow WW]]
-[[Category: Bourne, C R.]]
+[[Category: Bourne CR]]
-[[Category: Dihydrophthalazine]]
-[[Category: Oxidoreductase]]
-[[Category: Pyrimidine]]