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crystal structure of the tyrosine-regulated 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase from saccharomyces cerevisiae complexed with tyrosine and manganesecrystal structure of the tyrosine-regulated 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase from saccharomyces cerevisiae complexed with tyrosine and manganese
Structural highlights
Function[AROG_YEAST] Stereospecific condensation of phosphoenolpyruvate (PEP) and D-erythrose-4-phosphate (E4P) giving rise to 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Evolution of feedback-inhibited beta /alpha barrel isoenzymes by gene duplication and a single mutation.,Hartmann M, Schneider TR, Pfeil A, Heinrich G, Lipscomb WN, Braus GH Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):862-7. Epub 2003 Jan 22. PMID:12540830[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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