Quaternary structure sequence determinants in lumazine synthase

FORNASARI MS; LAPLAGNE DA; FRANKEL N; CAUERHFF A; GOLDBAUM FA; ECHAVE J

Bariloche, Rio Negro, Argentina

Congreso; XXXIX Reunión anual de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular (SAIB); 2003

Lumazine synthase catalyzes in microorganisms, fungi and plantsthe penultimate step of the riboflavin biosynthetic pathway. Themost distinctive characteristic of this enzyme is that it is found indifferent species in two different quaternary structures, pentamericand icosahedral, built from practically the same structuralmonomeric unit. Despite this difference, the active sites arevirtually identical in all structurally studied members.We present a combined analysis that includes sequence-structureand evolutionary studies to find the sequence determinants of thedifferent quaternary assemblies of this enzyme. Using similaritysearches, phylogenetic clustering, sequence conservation andpatterns of three-dimensional contacts derived from the known3D structures we found a significant shift in structural constraintsof certain positions. To analyze changes in structural/functionalconstraints, site-specific evolutionary rate shifts were alsoperformed. We found that the positions involved in icosahedralcontacts are not significantly more conserved than the rest whenicosahedral sequences are compared. However the comparisonbetween icosahedral and non-icosahedral representatives revealsthat the icosahedral contact positions suffer a larger constraintincrement than the positions not involved in this type of contact.Among the 27 icosahedral contact positions, 8 are postulated asthe most important icosahedral sequence determinants