L-myo-Inositol 1-phosphate synthase (MIPS, EC 126.96.36.199), the key enzyme in the inositol and phosphoinositide biosynthetic pathway, is present throughout evolutionarily diverse organisms and is considered an ancient protein/gene. Analysis by multiple sequence alignment, phylogenetic tree generation and comparison of newly determined crystal structures provides new insight into the origin and evolutionary relationships among the various MIPS proteins/genes. The evolution of the MIPS protein/gene among the prokaryotes seems more diverse and complex than amongst the eukaryotes. However, conservation of a 'core catalytic structure' among the MIPS proteins implies an essential function of the enzyme in cellular metabolism throughout the biological kingdom. © 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
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