Proteopedia

3pfp: Difference between revisions

← Older editNewer edit →
No edit summary
No edit summary
Line 1: Line 1:
[[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==
<StructureSection load='3pfp' size='340' side='right' caption='[[3pfp]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PFP FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2b7o|2b7o]], [[3nv8|3nv8]], [[3kgf|3kgf]], [[3nud|3nud]], [[3nue|3nue]]</td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">aroG, Rv2178c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-deoxy-7-phosphoheptulonate_synthase 3-deoxy-7-phosphoheptulonate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.54 2.5.1.54] </span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3pfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pfp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3pfp RCSB], [http://www.ebi.ac.uk/pdbsum/3pfp PDBsum]</span></td></tr>
<table>
<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.


<!--
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>
The line below this paragraph, containing "STRUCTURE_3pfp", 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_3pfp|  PDB=3pfp  |  SCENE=  }}


===Structure of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis in complex with an active site inhibitor===
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
 
</div>
 
== References ==
<!--
<references/>
The line below this paragraph, {{ABSTRACT_PUBMED_21454647}}, adds the Publication Abstract to the page
__TOC__
(as it appears on PubMed at http://www.pubmed.gov), where 21454647 is the PubMed ID number.
</StructureSection>
-->
{{ABSTRACT_PUBMED_21454647}}
 
==About this Structure==
[[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].
 
==Reference==
<ref group="xtra">PMID:021454647</ref><references group="xtra"/>
[[Category: 3-deoxy-7-phosphoheptulonate synthase]]
[[Category: 3-deoxy-7-phosphoheptulonate synthase]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/w/3pfp"