PhD Oral:- The long and short of DAH7PS: distinct quaternary structures of two type II isozymes from Pseudomonas aeruginosa
The Biomolecullar Interaction Centre and The School of Physical and Chemical Sciences, UC
Time & Place
Mon, 15 Oct 2018 11:00:00 NZDT in Room 443, Level 4
All are welcome
The shikimate pathway is responsible for the biosynthesis of key aromatic metabolites including the aromatic amino acids phenylalanine, tyrosine, and tryptophan. In Pseudomonas aeruginosa, the shikimate pathway end product, chorismate, serves as the last common precursor for the biosynthesis of both primary aromatic metabolites, including the aromatic amino acids, and secondary aromatic metabolites, including phenazine-1-carboxylic acid and pyocyanin.
The enzyme 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyses the first step of the shikimate pathway and is often subject to feedback inhibition by pathway end products. The allosteric binding sites are generally located in close proximity to the oligomeric interfaces and, as such, the quaternary structure plays a key role in the function and regulation of the enzyme. The presence of structural elements that are additional to the core catalytic domain influences the nature of the quaternary assembly and hence these structural elements are intricately related to the allosteric properties of the enzyme.
We have solved the structure of two distinct DAH7PS isozymes from P. aeruginosa, revealing for the first time the structure of a short form enzyme that is involved in pyocyanin biosynthesis. These structures illuminate the distinct quaternary assemblies that are likely associated with the unique allosteric properties of these enzymes providing new insights into the linkages between the active and allosteric sites. P. aeruginosa appears to have evolved control of shikimate pathway flux at the genetic level, rather than control by multiple allosteric effectors to a single type II DAH7PS, as is the case in M. tuberculosis. Type II DAH7PSs, thus, appear to have a more varied evolutionary trajectory than previously indicated.