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The enzyme 3\u2010deoxy\u2010<jats:sc>d<\/jats:sc>\u2010<jats:italic>arabino<\/jats:italic>\u2010heptulosonate 7\u2010phosphate synthase (DAH7PS) catalyzes the first reaction in the shikimate pathway leading to the biosynthesis of aromatic metabolites including the aromatic acids <jats:sc>l<\/jats:sc>\u2010Trp, <jats:sc>l<\/jats:sc>\u2010Phe, and <jats:sc>l<\/jats:sc>\u2010Tyr. 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 <jats:italic>N. meningitidis<\/jats:italic> was determined at 2.0 \u00c5 resolution. In contrast to the other DAH7PS enzymes, which are inhibited only by a single aromatic amino acid, the <jats:italic>N. meningitidis<\/jats:italic> DAH7PS was inhibited by all three aromatic amino acids, showing greatest sensitivity to <jats:sc>l<\/jats:sc>\u2010Phe. An <jats:italic>N. meningitidis<\/jats:italic> enzyme variant, in which a single Ser residue at the bottom of the inhibitor\u2010binding cavity was substituted to Gly, altered inhibitor specificity from <jats:sc>l<\/jats:sc>\u2010Phe to <jats:sc>l<\/jats:sc>\u2010Tyr. Comparison of the crystal structures of both unbound and Tyr\u2010bound forms and the small angle X\u2010ray scattering profiles reveal that <jats:italic>N. meningtidis<\/jats:italic> 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.<\/jats:p>","DOI":"10.1002\/pro.2293","type":"journal-article","created":{"date-parts":[[2013,6,11]],"date-time":"2013-06-11T10:08:40Z","timestamp":1370945320000},"page":"1087-1099","source":"Crossref","is-referenced-by-count":24,"title":["<i>Neisseria meningitidis<\/i> expresses a single 3\u2010deoxy\u2010<scp>d<\/scp>\u2010<i>arabino<\/i>\u2010heptulosonate 7\u2010phosphate synthase that is inhibited primarily by phenylalanine"],"prefix":"10.1002","volume":"22","author":[{"given":"Penelope J.","family":"Cross","sequence":"first","affiliation":[{"name":"Biomolecular Interaction Centre and Department of Chemistry University of Canterbury Christchurch New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy 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