2ypo: Difference between revisions
New page: '''Unreleased structure''' The entry 2ypo is ON HOLD Authors: Blackmore, N.J., Reichau, S., Jiao, W., Hutton, R.D., Baker, E.N., Jameson, G.B., Parker, E.J. Description: 3-deoxy-D-arab... |
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==3-deoxy-D-arabino-heptulosonate 7-phosphate synthase with phenylalanine bound in only one site== | |||
<StructureSection load='2ypo' size='340' side='right'caption='[[2ypo]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2ypo]] 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=2YPO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YPO 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]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PHE:PHENYLALANINE'>PHE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2ypo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ypo OCA], [https://pdbe.org/2ypo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ypo RCSB], [https://www.ebi.ac.uk/pdbsum/2ypo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ypo 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 == | |||
3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first step in the shikimate pathway, the pathway responsible for the biosynthesis of the aromatic amino acids, Trp, Phe and Tyr. Unlike many other organisms that produce up to three isozymes, each feedback-regulated by one of the aromatic amino acid pathway end-products, Mycobacterium tuberculosis expresses a single DAH7PS enzyme that can be controlled by combinations of aromatic amino acids. This study shows that the synergistic inhibition of this enzyme by a combination Trp and Phe can be significantly augmented by the addition of Tyr. We used X-ray crystallography, mutagenesis and isothermal titration calorimetry studies to show that DAH7PS from M. tuberculosis possesses a Tyr-selective site in addition to the Trp and Phe sites, revealing an unusual and highly sophisticated network of three synergistic allosteric sites on one enzyme. This ternary inhibitory response, by a combination of all three aromatic amino acids, allows a tunable response of the protein to changing metabolic demands. | |||
Three Sites and You Are Out: Ternary Synergistic Allostery Controls Aromatic Aminoacid Biosynthesis in Mycobacterium Tuberculosis.,Blackmore NJ, Reichau S, Jiao W, Hutton RD, Baker EN, Jameson GB, Parker EJ J Mol Biol. 2012 Dec 27. pii: S0022-2836(12)00952-7. doi:, 10.1016/j.jmb.2012.12.019. PMID:23274137<ref>PMID:23274137</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2ypo" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DAHP synthase 3D structures|DAHP synthase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis]] | |||
[[Category: Baker EN]] | |||
[[Category: Blackmore NJ]] | |||
[[Category: Hutton RD]] | |||
[[Category: Jameson GB]] | |||
[[Category: Jiao W]] | |||
[[Category: Parker EJ]] | |||
[[Category: Reichau S]] | |||
Latest revision as of 13:57, 20 December 2023
3-deoxy-D-arabino-heptulosonate 7-phosphate synthase with phenylalanine bound in only one site3-deoxy-D-arabino-heptulosonate 7-phosphate synthase with phenylalanine bound in only one site
Structural highlights
FunctionAROG_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 PubMed3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first step in the shikimate pathway, the pathway responsible for the biosynthesis of the aromatic amino acids, Trp, Phe and Tyr. Unlike many other organisms that produce up to three isozymes, each feedback-regulated by one of the aromatic amino acid pathway end-products, Mycobacterium tuberculosis expresses a single DAH7PS enzyme that can be controlled by combinations of aromatic amino acids. This study shows that the synergistic inhibition of this enzyme by a combination Trp and Phe can be significantly augmented by the addition of Tyr. We used X-ray crystallography, mutagenesis and isothermal titration calorimetry studies to show that DAH7PS from M. tuberculosis possesses a Tyr-selective site in addition to the Trp and Phe sites, revealing an unusual and highly sophisticated network of three synergistic allosteric sites on one enzyme. This ternary inhibitory response, by a combination of all three aromatic amino acids, allows a tunable response of the protein to changing metabolic demands. Three Sites and You Are Out: Ternary Synergistic Allostery Controls Aromatic Aminoacid Biosynthesis in Mycobacterium Tuberculosis.,Blackmore NJ, Reichau S, Jiao W, Hutton RD, Baker EN, Jameson GB, Parker EJ J Mol Biol. 2012 Dec 27. pii: S0022-2836(12)00952-7. doi:, 10.1016/j.jmb.2012.12.019. PMID:23274137[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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