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| | ==Crystal structure of DAH7PS from Neisseria meningitidis== | | ==Crystal structure of DAH7PS from Neisseria meningitidis== |
| - | <StructureSection load='4hsn' size='340' side='right' caption='[[4hsn]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4hsn' size='340' side='right'caption='[[4hsn]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hsn]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Neimb Neimb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HSN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HSN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hsn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_meningitidis_MC58 Neisseria meningitidis MC58]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HSN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HSN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEP:PHOSPHOENOLPYRUVATE'>PEP</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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hso|4hso]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEP:PHOSPHOENOLPYRUVATE'>PEP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">aroG, NMB0307 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=122586 NEIMB])</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=4hsn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hsn OCA], [https://pdbe.org/4hsn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hsn RCSB], [https://www.ebi.ac.uk/pdbsum/4hsn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hsn 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=4hsn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hsn OCA], [http://pdbe.org/4hsn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hsn RCSB], [http://www.ebi.ac.uk/pdbsum/4hsn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hsn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q9K169_NEIMB Q9K169_NEIMB]] Stereospecific condensation of phosphoenolpyruvate (PEP) and D-erythrose-4-phosphate (E4P) giving rise to 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) (By similarity).[PIRNR:PIRNR001361] | + | [https://www.uniprot.org/uniprot/Q9K169_NEIMB Q9K169_NEIMB] Stereospecific condensation of phosphoenolpyruvate (PEP) and D-erythrose-4-phosphate (E4P) giving rise to 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) (By similarity).[PIRNR:PIRNR001361] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[DAHP synthase|DAHP synthase]] | + | *[[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: Neimb]] | + | [[Category: Neisseria meningitidis MC58]] |
| - | [[Category: Allison, T M]] | + | [[Category: Allison TM]] |
| - | [[Category: Cochrane, F C]] | + | [[Category: Cochrane FC]] |
| - | [[Category: Cross, P J]] | + | [[Category: Cross PJ]] |
| - | [[Category: Parker, E J]] | + | [[Category: Parker EJ]] |
| - | [[Category: Pietersma, A L]] | + | [[Category: Pietersma AL]] |
| - | [[Category: Wilson-Coutts, S M]] | + | [[Category: Wilson-Coutts SM]] |
| - | [[Category: Allosteric regulation]]
| + | |
| - | [[Category: Aromatic biosynthesis]]
| + | |
| - | [[Category: Dah7p]]
| + | |
| - | [[Category: Dahp]]
| + | |
| - | [[Category: Shikimate pathway]]
| + | |
| - | [[Category: Tim barrel]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
Q9K169_NEIMB Stereospecific condensation of phosphoenolpyruvate (PEP) and D-erythrose-4-phosphate (E4P) giving rise to 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) (By similarity).[PIRNR:PIRNR001361]
Publication Abstract from PubMed
Neisseria meningitidis is the causative agent of meningitis and meningococcal septicemia is a major cause of disease worldwide, resulting in brain damage and hearing loss, and can be fatal in a large proportion of cases. The enzyme 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first reaction in the shikimate pathway leading to the biosynthesis of aromatic metabolites including the aromatic acids l-Trp, l-Phe, and l-Tyr. This pathway is absent in humans, meaning that enzymes of the pathway are considered as potential candidates for therapeutic intervention. As the entry point, feedback inhibition of DAH7PS by pathway end products is a key mechanism for the control of pathway flux. The structure of the single DAH7PS expressed by N. meningitidis was determined at 2.0 A resolution. In contrast to the other DAH7PS enzymes, which are inhibited only by a single aromatic amino acid, the N. meningitidis DAH7PS was inhibited by all three aromatic amino acids, showing greatest sensitivity to l-Phe. An N. meningitidis enzyme variant, in which a single Ser residue at the bottom of the inhibitor-binding cavity was substituted to Gly, altered inhibitor specificity from l-Phe to l-Tyr. Comparison of the crystal structures of both unbound and Tyr-bound forms and the small angle X-ray scattering profiles reveal that N. meningtidis DAH7PS undergoes no significant conformational change on inhibitor binding. These observations are consistent with an allosteric response arising from changes in protein motion rather than conformation, and suggest ligands that modulate protein dynamics may be effective inhibitors of this enzyme.
Neisseria meningitidis expresses a single 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase that is inhibited primarily by phenylalanine.,Cross PJ, Pietersma AL, Allison TM, Wilson-Coutts SM, Cochrane FC, Parker EJ Protein Sci. 2013 Aug;22(8):1087-99. doi: 10.1002/pro.2293. Epub 2013 Jun 27. PMID:23754471[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cross PJ, Pietersma AL, Allison TM, Wilson-Coutts SM, Cochrane FC, Parker EJ. Neisseria meningitidis expresses a single 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase that is inhibited primarily by phenylalanine. Protein Sci. 2013 Aug;22(8):1087-99. doi: 10.1002/pro.2293. Epub 2013 Jun 27. PMID:23754471 doi:10.1002/pro.2293
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