5UXO

Type II DAH7PS from Pseudomonas aeruginosa

Summary for 5UXO

• Entry DOI: 10.2210/pdb5uxo/pdb
• Related: 5UXM 5UXN
• Descriptor: Phospho-2-dehydro-3-deoxyheptonate aldolase, COBALT (II) ION, PHOSPHOENOLPYRUVATE, ... (6 entities in total)
• Functional Keywords: transferase, dah7ps, 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase, shikimate pathway
• Biological source: Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
• Total number of polymer chains: 1
• Total formula weight: 50554.30

Authors

Sterritt, O.W.,Jameson, G.B.,Parker, E.J. (deposition date: 2017-02-23, release date: 2018-02-28, Last modification date: 2024-11-06)

Primary citation

Sterritt, O.W.,Kessans, S.A.,Jameson, G.B.,Parker, E.J.
A Pseudoisostructural Type II DAH7PS Enzyme from Pseudomonas aeruginosa: Alternative Evolutionary Strategies to Control Shikimate Pathway Flux.
Biochemistry, 57:2667-2678, 2018

PubMed Abstract: The shikimate pathway is responsible for the biosynthesis of key aromatic metabolites in microorganisms and plants. The enzyme 3-deoxy-d- arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first step of the pathway and DAH7PSs are classified as either type I or type II. The DAH7PSs from Pseudomonas aeruginosa are of particular interest as open reading frames encoding four putative DAH7PS isoenzymes, two classified as type Iα and two classified as type II, have been identified. Here, the structure of a type II DAH7PS enzyme from P. aeruginosa (PAO1) has been determined at 1.54 Å resolution, in complex with its allosteric inhibitor tryptophan. Structural differences in the extra-barrel elements, when compared to other type II DAH7PS enzymes, directly relate to the formation of a distinct quaternary conformation with consequences for allosteric function and the control of flux to branching pathways. In contrast to the well-characterized Mycobacterium tuberculosis type II DAH7PS, which binds multiple allosteric inhibitors, this PaeDAH7PS is observed to be modestly allosterically inhibited by a single aromatic amino acid, tryptophan. In addition, structures in complex with tyrosine or with no allosteric ligand bound were determined. These structures provide new insights into the linkages between the active and allosteric sites. With four putative DAH7PS enzymes, 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 in M. tuberculosis. Type II DAH7PSs, thus, appear to have a more varied evolutionary trajectory than previously indicated.

PubMed: 29608284
DOI: 10.1021/acs.biochem.8b00082

Experimental method

X-RAY DIFFRACTION (2.35 Å)