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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 [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YPO FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ypp|2ypp]], [[2ypq|2ypq]]</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ypo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ypo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ypo RCSB], [http://www.ebi.ac.uk/pdbsum/2ypo PDBsum]</span></td></tr> | |||
</table> | |||
<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> | |||
== References == | |||
== | <references/> | ||
<references | __TOC__ | ||
</StructureSection> | |||
[[Category: 3-deoxy-7-phosphoheptulonate synthase]] | [[Category: 3-deoxy-7-phosphoheptulonate synthase]] | ||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Baker, E N | [[Category: Baker, E N]] | ||
[[Category: Blackmore, N J | [[Category: Blackmore, N J]] | ||
[[Category: Hutton, R D | [[Category: Hutton, R D]] | ||
[[Category: Jameson, G B | [[Category: Jameson, G B]] | ||
[[Category: Jiao, W | [[Category: Jiao, W]] | ||
[[Category: Parker, E J | [[Category: Parker, E J]] | ||
[[Category: Reichau, S | [[Category: Reichau, S]] | ||
[[Category: Aromatic amino acid biosynth allostery]] | [[Category: Aromatic amino acid biosynth allostery]] | ||
[[Category: Shikimate pathway]] | [[Category: Shikimate pathway]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Revision as of 17:06, 18 December 2014
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
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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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