X‐ray Crystal Structure of Agmatinase from Escherichia coli

Abstract

Agmatinase acts upon the cellular metabolite agmatine to produce putrescine, an important precursor for higher‐order polyamines that are required for cell proliferation, differentiation, and migration. The activity of agmatinase and the role of agmatine have garnered attention due to the importance of agmatine in various medical contexts including: neurological disorders, a possible role for agmatine as a neurotransmitter/neuromodulator, treatment of depression, and even the proposal that the family of metallohydrolases that include agmatinase may find novel biotechnological applications. Here we report the crystal structure of Escherichia coli agmatinase. The structure of E. coli agmatinase exhibits global fold and active site architecture typical of the metal‐dependent ureohydrolase protein superfamily. Moreover, the arrangement of conserved metal ligands and electron density at the active site indicate the presence of two metal ions, which is consistent with reported literature finding E. coli agmatinase to require two Mn2+ ions. Comparisons with the structures of related proteins will be described, along with functional characterization of agmatinase in terms of both enzymatic activity, as well as the requirement and identity of metal ions.