结构生物学sturcture biology explore-65.pdfVIP

374 Pathway evolution, structurally speaking Stuart CG Rison* and Janet M Thornton*†‡ Small-molecule metabolism forms the core of the metabolic evolving an enzyme that catalyses this synthesis will rapidly processes of all living organisms. As early as 1945, possible spread through the environment; in addition, in the mechanisms for the evolution of such a complex metabolic continued absence of environmental A, any null mutation system were considered. The problem is to explain the of the evolved enzyme will be lethal, thereby favouring its appearance and development of a highly regulated complex preservation. In turn, as the environmental concentration network of interacting proteins and substrates from a limited of B or C drops, the process will be repeated with the structural and functional repertoire. By permitting the similar recruitment of further enzymes. The retrograde co-analysis of phylogeny and metabolism, the combined model of pathway evolution is illustrated in Figure 1. In exploitation of pathway and structural databases, as well as the addition, Horowitz suggested that the simultaneous use of multiple-sequence alignment search algorithms, sheds unavailability of two intermediates (say B and C) would light on this problem. Much of the current research suggests a favour symbiotic association between two mutants, one chemistry-driven ‘patchwork’ model of pathway evolution, but capable of synthesising B and the other of synthesising C other mechanisms may play a role. In the future, as metabolic from other environmental precursors. structure and sequence space are further explored, it should become easier to trace the finer details of pathway However, the retr