1HFB

Crystal structure of the tyrosine-regulated 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Saccharomyces cerevisiae complexed with phosphoenolpyruvate

Summary for 1HFB

• Entry DOI: 10.2210/pdb1hfb/pdb
• Descriptor: TYROSINE-REGULATED 3-DEOXY-D-ARABINO-HEPTULOSONATE-7-PHOSPHATE SYNTHASE, PHOSPHOENOLPYRUVATE (3 entities in total)
• Functional Keywords: beta-alpha-barrel, lyase
• Biological source: SACCHAROMYCES CEREVISIAE
• Total number of polymer chains: 8
• Total formula weight: 319720.78

Authors

Schneider, T.R.,Hartmann, M.,Braus, G.H. (deposition date: 2000-11-30, release date: 2003-01-14, Last modification date: 2023-12-13)

Primary citation

Hartmann, M.,Schneider, T.R.,Pfeil, A.,Heinrich, G.,Lipscomb, W.,Braus, G.H.
Evolution of Feedback-Inhibited Beta /Alpha Barrel Isoenzymes by Gene Duplication and a Single Mutation
Proc.Natl.Acad.Sci.USA, 100:862-, 2003

PubMed Abstract: The betaalpha barrel is the common protein fold of numerous enzymes and was proposed recently to be the result of gene duplication and fusion of an ancient half-barrel. The initial enzyme of shikimate biosynthesis possesses the additional feature of feedback regulation. The crystal structure and kinetic studies on chimera and mutant proteins of yeast 3-deoxy-d-arabino-heptulosonate-7-phosphate (DAHP) synthase from Saccharomyces cerevisiae inhibited by phenylalanine (Aro3p) and DAHP synthase S. cerevisiae inhibited by tyrosine (Aro4p) give insight into important regions for regulation in the enzyme: The loop, which is connecting the two half-barrels, and structural elements added to the barrel are prerequisites for regulation and form a cavity on the N-terminal side of the betaalpha barrel. In the cavity of Aro4p at position 226 is a glycine residue, which is highly conserved in all other tyrosine-regulated DAHP synthases as well. Sequence alignments with phenylalanine-regulated DAHP synthases including Aro3p show a highly conserved serine residue at this position. An exchange of glycine to serine and vice versa leads to a complete change in the regulation pattern. Therefore the evolution of these differently feedback-inhibited isoenzymes required gene duplication and a single mutation within the internal extra element. Numerous additional amino acid substitutions present in the contemporary isoenzymes are irrelevant for regulation and occurred independently.

PubMed: 12540830
DOI: 10.1073/PNAS.0337566100

Experimental method

X-RAY DIFFRACTION (1.9 Å)