INVESTIGADORES
KLINKE Sebastian
artículos
Título:
High order quaternary arrangement confers increased structural stability to Brucella sp. lumazine synthase
Autor/es:
VANESA ZYLBERMAN; PATRICIO O. CRAIG; SEBASTIÁN KLINKE; BRADFORD C. BRADEN; ANA A. CAUERHFF; FERNANDO A. GOLDBAUM
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Editorial:
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Referencias:
Año: 2004 vol. 279 p. 8093 - 8101
ISSN:
0021-9258
Resumen:
The penultimate step in the pathway of riboflavin biosynthesis
is catalyzed by the enzyme lumazine synthase
(LS). One of the most distinctive characteristics of this
enzyme is the structural quaternary divergence found in
different species. The protein exists as pentameric and
icosahedral forms, built from practically the same structural
monomeric unit. The pentameric structure is
formed by five 18-kDa monomers, each extensively contacting
neighboring monomers. The icosahedrical structure
consists of 60 LS monomers arranged as 12 pentamers
giving rise to a capsid exhibiting icosahedral 532
symmetry. In all lumazine synthases studied, the topologically
equivalent active sites are located at the interfaces
between adjacent subunits in the pentameric modules.
The Brucella sp. lumazine synthase (BLS) sequence
clearly diverges from pentameric and icosahedric enzymes.
This unusual divergence prompted us to further
investigate its quaternary arrangement. In the present
work, we demonstrate by means of solution light scattering
and x-ray structural analyses that BLS assembles as a
very stable dimer of pentamers, representing a third category
of quaternary assembly for lumazine synthases. We
also describe by spectroscopic studies the thermodynamic
stability of this oligomeric protein and postulate
a mechanism for dissociation/unfolding of this macromolecular
assembly. The higher molecular order of BLS increases
its stability 20 °C compared with pentameric lumazine
synthases. The decameric arrangement described
in this work highlights the importance of quaternary interactions
in the stabilization of proteins.