title: Crystal structure of agmatinase reveals structural conservation and inhibition mechanism of the ureohydrolase superfamily.
abstract: Agmatine is the product of arginine decarboxylation and can be hydrolyzed by agmatinase to putrescine, the precursor for biosynthesis of higher polyamines, spermidine, and spermine. Besides being an intermediate in polyamine metabolism, recent findings indicate that agmatine may play important regulatory roles in mammals. Agmatinase is a binuclear manganese metalloenzyme and belongs to the ureohydrolase superfamily that includes arginase, formiminoglutamase, and proclavaminate amidinohydrolase. Compared with a wealth of structural information available for arginases, no three-dimensional structure of agmatinase has been reported. Agmatinase from Deinococcus radiodurans, a 304-residue protein, shows approximately 33% of sequence identity to human mitochondrial agmatinase. Here we report the crystal structure of D. radiodurans agmatinase in Mn(2+)-free, Mn(2+)-bound, and Mn(2+)-inhibitor-bound forms, representing the first structure of agmatinase. It reveals the conservation as well as variation in folding, oligomerization, and the active site of the ureohydrolase superfamily. D. radiodurans agmatinase exists as a compact homohexamer of 32 symmetry. Its binuclear manganese cluster is highly similar but not identical to the clusters of arginase and proclavaminate amidinohydrolase. The structure of the inhibited complex reveals that inhibition by 1,6-diaminohexane arises from the displacement of the metal-bridging water.
authors.affiliation: Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Ahn
authors.forename: Kyoung Hoon
authors.initials: KH
authors.lastname: Kim
authors.forename: Jiah
authors.initials: J
authors.lastname: Lee
authors.forename: Jun-Yong
authors.initials: JY
authors.lastname: Ha
authors.forename: Hyung Ho
authors.initials: HH
authors.lastname: Lee
authors.forename: Dojin
authors.initials: D
authors.lastname: Kim
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Ae-Ran
authors.initials: AR
authors.lastname: Kwon
authors.forename: Se Won
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000376:Agmatine / Q000378:metabolism*; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D034301:Deinococcus / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D014512:Ureohydrolases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000376:Agmatine; D014512:Ureohydrolases; C019625:agmatinase