title: Mammalian agmatinases constitute unusual members in the family of Mn2+-dependent ureahydrolases.
abstract: Agmatine (1-amino-4-guanidinobutane) plays an important role in a range of metabolic functions, in particular in the brain. Agmatinases (AGMs) are enzymes capable of converting agmatine to the polyamine putrescine and urea. AGMs belong to the family of Mn2+-dependent ureahydrolases. However, no AGM from a mammalian source has yet been extracted in catalytically active form. While in human AGM the six amino acid ligands that coordinate the two Mn2+ions in the active site are conserved, four mutations are observed in the murine enzyme. Here, we demonstrate that similar to its human counterpart murine AGM does not appear to have in vitro catalytic activity, independent of the presence of Mn2+. However, in presence of agmatine both enzymes are very efficient in promoting cell growth of a yeast strain that is deficient in polyamine biosynthesis (Saccharomyces cerevisiae strain TRY104Δspe1). Furthermore, mutations among the putative Mn2+binding residues had no effect on the ability of murine AGM to promote growth of the yeast culture. It thus appears that mammalian AGMs form a distinct group within the family of ureahydrolases that (i) either fold in a manner distinct from other members in this family, or (ii) require accessory proteins to bind Mn2+in a mechanism related to that observed for the Ni2+-dependent urease.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160-C, Concepción, Chile.
authors.forename: Nicol
authors.initials: N
authors.lastname: Romero
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160-C, Concepción, Chile.
authors.forename: José
authors.initials: J
authors.lastname: Benítez
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160-C, Concepción, Chile.
authors.forename: David
authors.initials: D
authors.lastname: Garcia
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160-C, Concepción, Chile.
authors.forename: Arlette
authors.initials: A
authors.lastname: González
authors.affiliation: Departamento de Física, Facultad de Ciencias Físicas y Matemáticas, Universidad de Concepción, Casilla 160-C, Concepción, Chile.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Bennun
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160-C, Concepción, Chile.
authors.forename: María A
authors.initials: MA
authors.lastname: García-Robles
authors.affiliation: Departamento de Ciencias Biomédicas, Universidad Católica del Norte, Coquimbo, Chile.
authors.forename: Vasthi
authors.initials: V
authors.lastname: López
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Liam A
authors.initials: LA
authors.lastname: Wilson
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schenk
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160-C, Concepción, Chile.
authors.forename: Nelson
authors.initials: N
authors.lastname: Carvajal
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160-C, Concepción, Chile. Electronic address: auribe@udec.cl.
authors.forename: Elena
authors.initials: E
authors.lastname: Uribe
mesh_terms: D000376:Agmatine / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D008345:Manganese / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D011994:Recombinant Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014512:Ureohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D008345:Manganese; D000376:Agmatine; D014512:Ureohydrolases; C019625:agmatinase
keywords: Agmatinase; Manganese binding; Neurotransmitter; Polyamine biosynthesis; Ureahydrolases