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| | ==DAHP synthase from Mycobacterium tuberculosis, fully inhibited by tyrosine, phenylalanine, and tryptophan== | | ==DAHP synthase from Mycobacterium tuberculosis, fully inhibited by tyrosine, phenylalanine, and tryptophan== |
| - | <StructureSection load='5ckv' size='340' side='right' caption='[[5ckv]], [[Resolution|resolution]] 2.79Å' scene=''> | + | <StructureSection load='5ckv' size='340' side='right'caption='[[5ckv]], [[Resolution|resolution]] 2.79Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ckv]] 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=5CKV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CKV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ckv]] 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=5CKV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CKV 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=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>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</scene>, <scene name='pdbligand=TYR:TYROSINE'>TYR</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]] 2.787Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nv8|3nv8]], [[2b7o|2b7o]], [[3kgf|3kgf]], [[3nud|3nud]], [[3nue|3nue]], [[3rzi|3rzi]], [[2ypp|2ypp]], [[2ypo|2ypo]], [[2ypq|2ypq]]</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=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>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</scene>, <scene name='pdbligand=TYR:TYROSINE'>TYR</scene></td></tr> |
| - | <tr id='gene'><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 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=5ckv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ckv OCA], [https://pdbe.org/5ckv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ckv RCSB], [https://www.ebi.ac.uk/pdbsum/5ckv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ckv ProSAT]</span></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=5ckv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ckv OCA], [http://pdbe.org/5ckv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ckv RCSB], [http://www.ebi.ac.uk/pdbsum/5ckv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ckv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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 5ckv" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5ckv" 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: Krengel, U]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Munack, S]] | + | [[Category: Krengel U]] |
| - | [[Category: Feedback inhibition]] | + | [[Category: Munack S]] |
| - | [[Category: Shikimate pathway]]
| + | |
| - | [[Category: Tim-barrel]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
5ckv is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.787Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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
DAHP synthase and chorismate mutase catalyze key steps in the shikimate biosynthetic pathway en route to aromatic amino acids. In Mycobacterium tuberculosis, chorismate mutase (MtCM; Rv0948c), located at the branch point towards phenylalanine and tyrosine, has poor activity on its own. However, it is efficiently activated by the first enzyme of the pathway, DAHP synthase (MtDS; Rv2178c), through formation of a non-covalent MtCM-MtDS complex. Here, we show how MtDS serves as an allosteric platform for feedback regulation of both enzymes, using X-ray crystallography, SAXS, SEC, and MALS. Crystal structures of the fully inhibited MtDS and the allosterically down-regulated MtCM-MtDS complex, solved at 2.8 and 2.7 A, respectively, reveal how effector binding at the internal MtDS subunit interfaces regulates the activity of MtDS and MtCM. While binding of all three metabolic end products to MtDS shuts down the entire pathway, the binding of phenylalanine jointly with tyrosine releases MtCM from the MtCM-MtDS complex, hence suppressing MtCM activation by 'inter-enzyme allostery'. This elegant regulatory principle, invoking a transient allosteric enzyme interaction, seems to be driven by dynamics and is likely a general strategy used by nature.
Remote Control by Inter-Enzyme Allostery: A Novel Paradigm for Regulation of the Shikimate Pathway.,Munack S, Roderer K, Okvist M, Kamarauskaite J, Sasso S, van Eerde A, Kast P, Krengel U J Mol Biol. 2016 Jan 8. pii: S0022-2836(16)00020-6. doi:, 10.1016/j.jmb.2016.01.001. PMID:26776476[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
- ↑ Munack S, Roderer K, Okvist M, Kamarauskaite J, Sasso S, van Eerde A, Kast P, Krengel U. Remote Control by Inter-Enzyme Allostery: A Novel Paradigm for Regulation of the Shikimate Pathway. J Mol Biol. 2016 Jan 8. pii: S0022-2836(16)00020-6. doi:, 10.1016/j.jmb.2016.01.001. PMID:26776476 doi:http://dx.doi.org/10.1016/j.jmb.2016.01.001
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