View source for 4hso


==Crystal structure of S213G variant DAH7PS from Neisseria meningitidis==
<StructureSection load='4hso' size='340' side='right'caption='[[4hso]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4hso]] 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=4HSO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HSO 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]] 2.1&#8491;</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=TYR:TYROSINE'>TYR</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=4hso FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hso OCA], [https://pdbe.org/4hso PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hso RCSB], [https://www.ebi.ac.uk/pdbsum/4hso PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hso ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== 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<ref>PMID:23754471</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4hso" style="background-color:#fffaf0;"></div>

==See Also==
*[[DAHP synthase 3D structures|DAHP synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Neisseria meningitidis MC58]]
[[Category: Allison TM]]
[[Category: Cochrane FC]]
[[Category: Cross PJ]]
[[Category: Parker EJ]]
[[Category: Pietersma AL]]
[[Category: Wilson-Coutts SM]]