title: Structure of malonamidase E2 reveals a novel Ser-cisSer-Lys catalytic triad in a new serine hydrolase fold that is prevalent in nature.
abstract: A large group of hydrolytic enzymes, which contain a conserved stretch of approximately 130 amino acids designated the amidase signature (AS) sequence, constitutes a super family that is distinct from any other known hydrolase family. AS family enzymes are widespread in nature, ranging from bacteria to humans, and exhibit a variety of biological functions. Here we report the first structure of an AS family enzyme provided by the crystal structure of malonamidase E2 from Bradyrhizobium japonicum. The structure, representing a new protein fold, reveals a previously unidentified Ser-cisSer-Lys catalytic machinery that is absolutely conserved throughout the family. This family of enzymes appears to be evolutionarily distinct but has diverged to acquire a wide spectrum of individual substrate specificities, while maintaining a core structure that supports the catalytic function of the unique triad. Based of the structures of the enzyme in two different inhibited states, an unusual action mechanism of the triad is proposed that accounts for the role of the cis conformation in the triad.
authors.affiliation: National Creative Research Initiative Center for Biomolecular Recognition, Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Korea.
authors.forename: Sejeong
authors.initials: S
authors.lastname: Shin
authors.forename: Tae-Hee
authors.initials: TH
authors.lastname: Lee
authors.forename: Nam-Chul
authors.initials: NC
authors.lastname: Ha
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Koo
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Heung-Soo
authors.initials: HS
authors.lastname: Lee
authors.forename: Yu Sam
authors.initials: YS
authors.lastname: Kim
authors.forename: Byung-Ha
authors.initials: BH
authors.lastname: Oh
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D020369:Bradyrhizobium / Q000201:enzymology*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism; D007477:Ions; D008239:Lysine / Q000737:chemistry*; D008314:Malonates / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D007477:Ions; D008314:Malonates; D012694:Serine; C030290:malonic acid; D000581:Amidohydrolases; C064615:malonamidase E2 protein, Bradyrhizobium japonicum; D008239:Lysine