2qk8: Difference between revisions

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-[[Image:2qk8.jpg|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_2qk8", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
--->
-{{STRUCTURE_2qk8|  PDB=2qk8  |  SCENE=  }}
-'''Crystal structure of the anthrax drug target, Bacillus anthracis dihydrofolate reductase'''
+==Crystal structure of the anthrax drug target, Bacillus anthracis dihydrofolate reductase==
+<StructureSection load='2qk8' size='340' side='right'caption='[[2qk8]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2qk8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis_str._Sterne Bacillus anthracis str. Sterne]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QK8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QK8 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=MTX:METHOTREXATE'>MTX</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=2qk8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qk8 OCA], [https://pdbe.org/2qk8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qk8 RCSB], [https://www.ebi.ac.uk/pdbsum/2qk8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qk8 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/qk/2qk8_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=2qk8 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Spores of Bacillus anthracis are the infectious agent of anthrax. Current antibiotic treatments are limited due to resistance and patient age restrictions; thus, additional targets for therapeutic intervention are needed. One possible candidate is dihydrofolate reductase (DHFR), a biosynthetic enzyme necessary for anthrax pathogenicity. We determined the crystal structure of DHFR from B. anthracis (baDHFR) in complex with methotrexate (MTX; 1) at 2.4 Angstrom resolution. The structure reveals the crucial interactions required for MTX binding and a putative molecular basis for how baDHFR has natural resistance to trimethoprim (TMP; 2). The structure also allows insights for designing selective baDHFR inhibitors that will have weak affinities for the human enzyme. Additionally, we have found that 5-nitro-6-methylamino-isocytosine (MANIC; 3), which inhibits another B. anthracis folate synthesis enzyme, dihydropteroate synthase (DHPS), can also inhibit baDHFR. This provides a starting point for designing multi-target inhibitors that are less likely to induce drug resistance.
-==Overview==
+Crystal structure of the anthrax drug target, Bacillus anthracis dihydrofolate reductase.,Bennett BC, Xu H, Simmerman RF, Lee RE, Dealwis CG J Med Chem. 2007 Sep 6;50(18):4374-81. Epub 2007 Aug 14. PMID:17696333<ref>PMID:17696333</ref>
-Spores of Bacillus anthracis are the infectious agent of anthrax. Current antibiotic treatments are limited due to resistance and patient age restrictions; thus, additional targets for therapeutic intervention are needed. One possible candidate is dihydrofolate reductase (DHFR), a biosynthetic enzyme necessary for anthrax pathogenicity. We determined the crystal structure of DHFR from B. anthracis (baDHFR) in complex with methotrexate (MTX; 1) at 2.4 Angstrom resolution. The structure reveals the crucial interactions required for MTX binding and a putative molecular basis for how baDHFR has natural resistance to trimethoprim (TMP; 2). The structure also allows insights for designing selective baDHFR inhibitors that will have weak affinities for the human enzyme. Additionally, we have found that 5-nitro-6-methylamino-isocytosine (MANIC; 3), which inhibits another B. anthracis folate synthesis enzyme, dihydropteroate synthase (DHPS), can also inhibit baDHFR. This provides a starting point for designing multi-target inhibitors that are less likely to induce drug resistance.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-QK8 is a [[Single protein]] structure of 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=2QK8 OCA].
+</div>
+<div class="pdbe-citations 2qk8" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Crystal structure of the anthrax drug target, Bacillus anthracis dihydrofolate reductase., Bennett BC, Xu H, Simmerman RF, Lee RE, Dealwis CG, J Med Chem. 2007 Sep 6;50(18):4374-81. Epub 2007 Aug 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17696333 17696333]
+*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
-[[Category: Bacillus anthracis]]
+== References ==
-[[Category: Dihydrofolate reductase]]
+<references/>
-[[Category: Single protein]]
+__TOC__
-[[Category: Bennett, B C.]]
+</StructureSection>
-[[Category: Dealwis, C G.]]
+[[Category: Bacillus anthracis str. Sterne]]
-[[Category: Lee, R E.]]
+[[Category: Large Structures]]
-[[Category: Simmerman, R F.]]
+[[Category: Bennett BC]]
-[[Category: Xu, H.]]
+[[Category: Dealwis CG]]
-[[Category: Methotrexate]]
+[[Category: Lee RE]]
-[[Category: Nucleotide phosphate binding]]
+[[Category: Simmerman RF]]
-[[Category: Oxidoreductase]]
+[[Category: Xu H]]
-[[Category: Pseudo-rossman fold]]
-[[Category: Pteridine binding]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 15:06:22 2008''