Hiroshi Miyoshi

St. Marianna University School of Medicine; Kawasaki, Japan

Miyoshi H et al. (2002) EMBO J "Discrimination between mono- and trimethylated cap structures by two isoforms of Caenorhabditis elegans eIF4E."

Rhoads RE, Keiper BD, Darzynkiewicz E, Jankowska-Anyszka M, Dwyer DS, Miyoshi H

[EMBO J, 2002]

Primitive eukaryotes like Caenorhabditis elegans produce mRNAs capped with either m(7)GTP or m(3)(2,2,7)GTP. Caenorhabditis elegans also expresses five isoforms of the cap-binding protein eIF4E. Some isoforms (e.g. IFE-3) bind to m(7)GTP-Sepharose exclusively, whereas others (e.g. IFE-5) bind to both m(7)GTP- and m(3)(2,2,7)GTP-Sepharose. To examine specificity differences, we devised molecular models of the tertiary structures of IFE-3 and IFE-5, based on the known structure of mouse eIF4E-1. We then substituted amino acid sequences of IFE-5 with homologous sequences from IFE-3. As few as two changes (N64Y/V65L) converted the cap specificity of IFE-5 to essentially that of IFE-3. Molecular dynamics simulations suggested that the width and depth of the cap-binding cavity were larger in IFE-5 than in IFE-3 or the N64Y/V65L variant, supporting a model in which IFE-3 discriminates against m(3)(2,2,7)GTP by steric hindrance. Furthermore, the affinity of IFE-5 (but not IFE-3) for m(3)(2,2,7)GTP was reversibly increased when thiol reagents were removed. This was correlated with the formation of a disulfide bond between Cys-122 and Cys-126. Thus, translation of m(3)(2,2,7)GTP-capped mRNAs may be regulated by intracellular redox state.

Hideto Miyoshi

Miyoshi muscular dystrophy 1

A Miyoshi muscular dystrophy that has_material_basis_in mutation in the DYSF gene on chromosome 2p13.

Miyoshi muscular dystrophy 3

A Miyoshi muscular dystrophy that has_material_basis_in mutation in the ANO5 gene on chromosome 11p14.

Miyoshi muscular dystrophy 2

A Miyoshi muscular dystrophy characterized by asymmetric presentation of muscle weakness and atrophy that has_material_basis_in a locus on chromosome 10.

obsolete quinate/shikimate dehydrogenase activity

OBSOLETE. Catalysis of the reactions: L-quinate + NAD(P)+ = 3-dehydroquinate + NAD(P)H + H+, and shikimate + NAD(P)+ = 3-dehydroshikimate + NAD(P)H + H+.

obsolete 3,4-dihydroxyphenanthrene dioxygenase activity

OBSOLETE. Catalysis of the reaction: 3,4-dihydroxyphenanthrene + O2 = H+ + 2-hydroxy-2 H-benzo[h]chromene-2-carboxylate.

aromatic-L-amino-acid decarboxylase activity

Catalysis of the reaction: L-amino acid + H+ = R-H + CO2.

obsolete NAD(P)+ transhydrogenase activity

OBSOLETE. Catalysis of the reaction: NADPH + H+ + NAD+ = NADP+ + NADH + H+.