Molecular evolution of an oligomeric biocatalyst functioning in lysine biosynthesis
Dihydrodipicolinate synthase (DHDPS) is critical to the production of lysine through the diaminopimelate (DAP) pathway. Elucidation of the function, regulation and structure of this key class I aldolase has been the focus of considerable study in recent years, given that the dapA gene encoding DHDPS has been found to be essential to bacteria and plants. Allosteric inhibition by lysine is observed for DHDPS from plants and some bacterial species, the latter requiring a histidine or glutamate at position 56 (Escherichia coli numbering) over a basic amino acid. Structurally, two DHDPS monomers form the active site, which binds pyruvate and (S)-aspartate β-semialdehyde, with most dimers further dimerising to form a tetrameric arrangement around a solvent-filled centre cavity. The architecture and behaviour of these dimer-of-dimers is explored in detail, including biophysical studies utilising analytical ultracentrifugation, small-angle X-ray scattering and macromolecular crystallography that show bacterial DHDPS tetramers adopt a head-to-head quaternary structure, compared to the back-to-back arrangement observed for plant DHDPS enzymes. Finally, the potential role of pyruvate in providing substrate-mediated stabilisation of DHDPS is considered.
KeywordsAllostery Antibiotic Crystal Herbicide SAXS Sedimentation
We would like to thank the present and past members of the Perugini laboratory for their contributions over the past 15 years and their helpful discussions during the preparation of this review. We also acknowledge the Australian Synchrotron and the La Trobe University—Comprehensive Proteomics Platform for providing infrastructure that has supported the primary research reviewed here, and the Australian Research Council, Defence Threat Reduction Agency, La Trobe University Research Focus Area—Securing Food, Water & the Environment, and National Health & Medical Research Council for contributing to funding over the past 15 years to the research described in this review.
Compliance with ethical standards
Conflict of interest
Tatiana P. Soares da Costa declares that she has no conflict of interest. Belinda M. Abbott declares that she has no conflict of interest. Anthony R. Gendall declares that he has no conflict of interest. Santosh Panjikar declares that he has no conflict of interest. Matthew A. Perugini declares that he has no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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