View source for 5e7z


==3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis in complex with D/L-tryptophan and D-phenylalanine==
<StructureSection load='5e7z' size='340' side='right'caption='[[5e7z]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5e7z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E7Z OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5E7Z FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=DTR:D-TRYPTOPHAN'>DTR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nv8|3nv8]], [[3kgf|3kgf]], [[3rzi|3rzi]], [[2ypo|2ypo]], [[5e2l|5e2l]], [[5e40|5e40]], [[5e4n|5e4n]], [[5e5g|5e5g]], [[2ypq|2ypq]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">aroG_1, ERS024751_03564, ERS094182_00944, ERS124362_02783 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
<tr id='activity'><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 id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5e7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e7z OCA], [http://pdbe.org/5e7z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e7z RCSB], [http://www.ebi.ac.uk/pdbsum/5e7z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e7z ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Chirality plays a major role in recognition and interaction of biologically important molecules. The enzyme 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS) is the first enzyme of the shikimate pathway, which is responsible for the synthesis of aromatic amino acids in bacteria and plants, and a potential target for the development of antibiotics and herbicides. DAH7PS from Mycobacterium tuberculosis (MtuDAH7PS) displays an unprecedented complexity of allosteric regulation, with three interdependent allosteric binding sites and a ternary allosteric response to combinations of the aromatic amino acids l-Trp, l-Phe and l-Tyr. In order to further investigate the intricacies of this system and identify key residues in the allosteric network of MtuDAH7PS, we studied the interaction of MtuDAH7PS with aromatic amino acids that bear the non-natural d-configuration, and showed that the d-amino acids do not elicit an allosteric response. We investigated the binding mode of d-amino acids using X-ray crystallography, site directed mutagenesis and isothermal titration calorimetry. Key differences in the binding mode were identified: in the Phe site, a hydrogen bond between the amino group of the allosteric ligands to the side chain of Asn175 is not established due to the inverted configuration of the ligands. In the Trp site, d-Trp forms no interaction with the main chain carbonyl group of Thr240 and less favourable interactions with Asn237 when compared to the l-Trp binding mode. Investigation of the MtuDAH7PSN175A variant further supports the hypothesis that the lack of key interactions in the binding mode of the aromatic d-amino acids are responsible for the absence of an allosteric response, which gives further insight into which residues of MtuDAH7PS play a key role in the transduction of the allosteric signal.

Probing the Sophisticated Synergistic Allosteric Regulation of Aromatic Amino Acid Biosynthesis in Mycobacterium tuberculosis Using -Amino Acids.,Reichau S, Blackmore NJ, Jiao W, Parker EJ PLoS One. 2016 Apr 29;11(4):e0152723. doi: 10.1371/journal.pone.0152723., eCollection 2016. PMID:27128682<ref>PMID:27128682</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5e7z" style="background-color:#fffaf0;"></div>

==See Also==
*[[DAHP synthase 3D structures|DAHP synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: 3-deoxy-7-phosphoheptulonate synthase]]
[[Category: Large Structures]]
[[Category: Jiao, W]]
[[Category: Parker, E J]]
[[Category: Reichau, S]]
[[Category: Allosteric regulation]]
[[Category: Shikimate pathway]]
[[Category: Transferase]]