title: The diversity of allosteric controls at the gateway to aromatic amino acid biosynthesis.
abstract: Present within bacteria, plants, and some lower eukaryotes 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHPS) catalyzes the first committed step in the synthesis of a number of metabolites, including the three aromatic amino acids phenylalanine, tyrosine, and tryptophan. Catalyzing the first reaction in an important biosynthetic pathway, DAHPS is situated at a critical regulatory checkpoint-at which pathway input can be efficiently modulated to respond to changes in the concentration of pathway outputs. Based on a phylogenetic classification scheme, DAHPSs have been divided into three major subtypes (Iα, Iβ, and II). These subtypes are subjected to an unusually diverse pattern of allosteric regulation, which can be used to further subdivide the enzymes. Crystal structures of most of the regulatory subclasses have been determined. When viewed collectively, these structures illustrate how distinct mechanisms of allostery are applied to a common catalytic scaffold. Here, we review structural revelations regarding DAHPS regulation and make the case that the functional difference between the three major DAHPS subtypes relates to basic distinctions in quaternary structure and mechanism of allostery.
authors: Center for Structural Genomics of Infectious Diseases and Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors: Samuel H
authors: SH
authors: Light
authors: Wayne F
authors: WF
authors: Anderson
mesh_terms: D010723:3-Deoxy-7-Phosphoheptulonate Synthase / Q000737:chemistry* / Q000378:metabolism*; D000494:Allosteric Regulation; D024322:Amino Acids, Aromatic / Q000096:biosynthesis* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D025461:Feedback, Physiological; D008958:Models, Molecular
chemical_list: D024322:Amino Acids, Aromatic; D001426:Bacterial Proteins; D010723:3-Deoxy-7-Phosphoheptulonate Synthase
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