3pfp: Difference between revisions

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-[[Image:3pfp.png|left|200px]]
-<!--
+==Structure of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis in complex with an active site inhibitor==
-The line below this paragraph, containing "STRUCTURE_3pfp", creates the "Structure Box" on the page.
+<StructureSection load='3pfp' size='340' side='right'caption='[[3pfp]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3pfp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PFP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PFP FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=035:(2S)-2,7-BIS(PHOSPHONOOXY)HEPTANOIC+ACID'>035</scene>, <scene name='pdbligand=036:(2R)-2,7-BIS(PHOSPHONOOXY)HEPTANOIC+ACID'>036</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-{{STRUCTURE_3pfp|  PDB=3pfp  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3pfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pfp OCA], [https://pdbe.org/3pfp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pfp RCSB], [https://www.ebi.ac.uk/pdbsum/3pfp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pfp ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/AROG_MYCTU AROG_MYCTU] Catalyzes an aldol-like condensation reaction between phosphoenolpyruvate (PEP) and D-erythrose 4-phosphate (E4P) to generate 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAH7P) and inorganic phosphate.<ref>PMID:16288916</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Tuberculosis remains a serious global health threat, with the emergence of multidrug-resistant strains highlighting the urgent need for novel antituberculosis drugs. The enzyme 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first step of the shikimate pathway for the biosynthesis of aromatic compounds. This pathway has been shown to be essential in Mycobacterium tuberculosis, the pathogen responsible for tuberculosis. DAH7PS catalyzes a condensation reaction between P-enolpyruvate and erythrose 4-phosphate to give 3-deoxy-D-arabino-heptulosonate 7-phosphate. The enzyme reaction mechanism is proposed to include a tetrahedral intermediate, which is formed by attack of an active site water on the central carbon of P-enolpyruvate during the course of the reaction. Molecular modeling of this intermediate into the active site reported in this study shows a configurational preference consistent with water attack from the re face of P-enolpyruvate. Based on this model, we designed and synthesized an inhibitor of DAH7PS that mimics this reaction intermediate. Both enantiomers of this intermediate mimic were potent inhibitors of M. tuberculosis DAH7PS, with inhibitory constants in the nanomolar range. The crystal structure of the DAH7PS-inhibitor complex was solved to 2.35 A. Both the position of the inhibitor and the conformational changes of active site residues observed in this structure correspond closely to the predictions from the intermediate modeling. This structure also identifies a water molecule that is located in the appropriate position to attack the re face of P-enolpyruvate during the course of the reaction, allowing the catalytic mechanism for this enzyme to be clearly defined.
-===Structure of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis in complex with an active site inhibitor===
+Potent inhibitors of a shikimate pathway enzyme from Mycobacterium tuberculosis: combining mechanism- and modeling-based design.,Reichau S, Jiao W, Walker SR, Hutton RD, Baker EN, Parker EJ J Biol Chem. 2011 May 6;286(18):16197-207. Epub 2011 Mar 15. PMID:21454647<ref>PMID:21454647</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3pfp" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-[[3pfp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PFP OCA].
+*[[DAHP synthase 3D structures|DAHP synthase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:021454647</ref><references group="xtra"/>
+__TOC__
-[[Category: 3-deoxy-7-phosphoheptulonate synthase]]
+</StructureSection>
-[[Category: Mycobacterium tuberculosis]]
+[[Category: Large Structures]]
-[[Category: Baker, E N.]]
-[[Category: Hutton, R D.]]
-[[Category: Jiao, W.]]
-[[Category: Parker, E J.]]
-[[Category: Reichau, S.]]
-[[Category: Walker, S R.]]
-[[Category: Aromatic biosynthesis]]
-[[Category: Dah7p synthase]]
 [[Category: Mycobacterium tuberculosis]]
-[[Category: Shikimate pathway]]
+[[Category: Baker EN]]
-[[Category: Tim barrel]]
+[[Category: Hutton RD]]
-[[Category: Transferase-transferase inhibitor complex]]
+[[Category: Jiao W]]
+[[Category: Parker EJ]]
+[[Category: Reichau S]]
+[[Category: Walker SR]]