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| | ==3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis with D-tyrosine bound in the tyrosine and phenylalanine binding sites== | | ==3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis with D-tyrosine bound in the tyrosine and phenylalanine binding sites== |
| - | <StructureSection load='5e4n' size='340' side='right' caption='[[5e4n]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='5e4n' size='340' side='right'caption='[[5e4n]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5e4n]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E4N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E4N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5e4n]] 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=5E4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E4N FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DTY:D-TYROSINE'>DTY</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nv8|3nv8]], [[5e40|5e40]], [[2ypp|2ypp]], [[5e2l|5e2l]], [[3kgf|3kgf]], [[2ypq|2ypq]], [[3nud|3nud]], [[3nue|3nue]], [[3rzi|3rzi]], [[2ypo|2ypo]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DTY:D-TYROSINE'>DTY</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5e4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e4n OCA], [https://pdbe.org/5e4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e4n RCSB], [https://www.ebi.ac.uk/pdbsum/5e4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e4n ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5e4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e4n OCA], [http://pdbe.org/5e4n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e4n RCSB], [http://www.ebi.ac.uk/pdbsum/5e4n PDBsum]</span></td></tr> | + | |
| | </table> | | </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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5e4n" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5e4n" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DAHP synthase 3D structures|DAHP synthase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 3-deoxy-7-phosphoheptulonate synthase]] | + | [[Category: Large Structures]] |
| - | [[Category: Jiao, W]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Parker, E J]] | + | [[Category: Jiao W]] |
| - | [[Category: Reichau, S]] | + | [[Category: Parker EJ]] |
| - | [[Category: 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase]] | + | [[Category: Reichau S]] |
| - | [[Category: Allosteric regulation]]
| + | |
| - | [[Category: Amino acid]]
| + | |
| - | [[Category: Shikimate pathway]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
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.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Webby CJ, Baker HM, Lott JS, Baker EN, Parker EJ. The structure of 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis reveals a common catalytic scaffold and ancestry for type I and type II enzymes. J Mol Biol. 2005 Dec 9;354(4):927-39. Epub 2005 Oct 21. PMID:16288916 doi:10.1016/j.jmb.2005.09.093
- ↑ Reichau S, Blackmore NJ, Jiao W, Parker EJ. Probing the Sophisticated Synergistic Allosteric Regulation of Aromatic Amino Acid Biosynthesis in Mycobacterium tuberculosis Using -Amino Acids. PLoS One. 2016 Apr 29;11(4):e0152723. doi: 10.1371/journal.pone.0152723., eCollection 2016. PMID:27128682 doi:http://dx.doi.org/10.1371/journal.pone.0152723
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