title: Hydration and conformational equilibrium in yeast thioredoxin 1: implication for H(+) exchange.
abstract: One of the ancestral features of thioredoxins is the presence of a water cavity. Here, we report that a largely hydrated, conserved, buried aspartic acid in the water cavity modulates the dynamics of the interacting loops of yeast thioredoxin 1 (yTrx1). It is well-established that the aspartic acid, Asp24 for yTrx1, works as a proton acceptor in the reduction of the target protein. We propose a complementary role for Asp24 of coupling hydration and conformational motion of the water cavity and interacting loops. The intimate contact between the water cavity and the interacting loops means that motion at the water cavity will affect the interacting loops and vice versa. The D24N mutation alters the conformational equilibrium for both the oxidized and reduced states, quenching the conformational motion in the water cavity. By measuring the hydration and molecular dynamics simulation of wild-type yTrx1 and the D24N mutant, we showed that Asn24 is more exposed to water than Asp24 and the water cavity is smaller in the mutant, closing the inner part of the water cavity. We discuss how the conformational equilibrium contributes to the mechanism of catalysis and H(+) exchange.
authors.affiliation: Institute of Medical Biochemistry, National Center of Nuclear Magnetic Resonance Jiri Jonas, Federal University of Rio de Janeiro-Institute of Structural Biology and Bioimaging , Rio de Janeiro, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Cruzeiro-Silva
authors.forename: Francisco
authors.initials: F
authors.lastname: Gomes-Neto
authors.forename: Luciana E S F
authors.initials: LE
authors.lastname: Machado
authors.forename: Catarina A
authors.initials: CA
authors.lastname: Miyamoto
authors.forename: Anderson S
authors.initials: AS
authors.lastname: Pinheiro
authors.forename: Natalia
authors.initials: N
authors.lastname: Correa-Pereira
authors.forename: Mariana T Q
authors.initials: MT
authors.lastname: de Magalhães
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Valente
authors.forename: Fabio C L
authors.initials: FC
authors.lastname: Almeida
mesh_terms: D001216:Asparagine / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D011522:Protons; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013879:Thioredoxins / Q000737:chemistry* / Q000235:genetics; D014867:Water
chemical_list: D011522:Protons; D014867:Water; D001224:Aspartic Acid; D013879:Thioredoxins; D001216:Asparagine