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The ␤͞␣ 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 ␤͞␣ 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. The ␤͞␣ barrel is the typical protein fold of a large number of enzymes (1). Evolution of these enzymes is the result of the divergent evolution of a common ancestral barrel, the convergent evolution to a stable three-dimensional structure, or a combination of both. The recent comparison of the ␤͞␣ barrel structures of two histidine biosynthetic enzymes strongly suggests that these molecules have evolved from an ancestral half-barrel by tandem duplication and fusion (2, 3). For the biosynthesis of the aromatic amino acid tryptophan, most protein structures have been determined and are predominantly folded as eightfold ␤͞␣ barrels. Many of these enzymes might be the result of gene duplication and gene fusion events and subsequent amino acid substitutions. In addition, distinct protein-protein interactions have been evolved, allowing the formation of oligomeric enzymes (4). The evolution of different enzyme activities requires appropriate changes in the catalytic center of the enzymes, which is localized on the C-terminal face of the central eight-stranded ␤ barrel.Gene duplication and subsequent alteration can be analyzed in a contemporary cell by comparing isogenes and the corresponding isoenzymes, which are a considerable part of all known enzymes (5). Amino acid sequences of isoenzymes are usually highly similar and allow studies on domains, which have been conserved during the course of evolution.The initial step of aromatic amino acid biosynthesis is the condensation of erythrose-4-phosphate and phosphoenolpyruvate (PEP), resulting in 3-deoxy-D-arabino-heptulosonate...

We present observations and dynamical models of the stellar nuclear clusters (NCs) at the centres of NGC 4244 and M33. We then compare these to an extensive set of simulations testing the importance of purely stellar dynamical mergers on the formation and growth of NCs. Mergers of star clusters are able to produce a wide variety of observed properties, including densities, structural scaling relations, shapes (including the presence of young discs) and even rapid rotation. None the less, difficulties remain, most notably that the second‐order kinematic moment of the models is too centrally peaked to match observations. This can be partially remedied by the merger of star clusters on to a pre‐existing nuclear disc, but the line‐of‐sight velocity V is still more slowly rising than in NGC 4244. Our results therefore suggest that purely stellar dynamical mergers cannot form NCs and that gas dissipation is a necessary ingredient for at least ∼50 per cent of a NC’s mass. The negative vertical anisotropy found in NGC 4244, however, requires at least 10 per cent of the mass to have been accreted as stars, since gas dissipation and in situ star formation leads to positive vertical anisotropy.