title: Structure and mechanism of an antibiotics-synthesizing 3-hydroxykynurenine C-methyltransferase.
abstract: Streptosporangium sibiricum SibL catalyzes the methyl transfer from S-adenosylmethionine (SAM) to 3-hydroxykynurenine (3-HK) to produce S-adenosylhomocysteine (SAH) and 3-hydroxy-4-methyl-kynurenine for sibiromycin biosynthesis. Here, we present the crystal structures of apo-form Ss-SibL, Ss-SibL/SAH binary complex and Ss-SibL/SAH/3-HK ternary complex. Ss-SibL is a homodimer. Each subunit comprises a helical N-terminal domain and a Rossmann-fold C-terminal domain. SAM (or SAH) binding alone results in domain movements, suggesting a two-step catalytic cycle. Analyses of the enzyme-ligand interactions and further mutant studies support a mechanism in which Tyr134 serves as the principal base in the transferase reaction of methyl group from SAM to 3-HK.
authors.affiliation: 1] Department of Biotechnology, Hungkuang University, Taichung, Taiwan [2] Taiwan Advance Biopharm (TABP), Inc., Xizhi City, New Taipei City, Taiwan.
authors.forename: Sheng-Chia
authors.initials: SC
authors.lastname: Chen
authors.affiliation: 1] Department of Biotechnology, Hungkuang University, Taichung, Taiwan [2] Taiwan Advance Biopharm (TABP), Inc., Xizhi City, New Taipei City, Taiwan.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Shu-Jung
authors.initials: SJ
authors.lastname: Lai
authors.affiliation: Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Jai-Shin
authors.initials: JS
authors.lastname: Liu
authors.affiliation: 1] Division of Critical Care &Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan [2] Department of Applied Chemistry, National Chi Nan University, Nantou County, Taiwan.
authors.forename: Pin-Kuei
authors.initials: PK
authors.lastname: Fu
authors.affiliation: 1] Department of Food and Nutrition, Providence University, Taichung, Taiwan [2] Department of Endocrinology and Metabolism, Kuang Tien General Hospital, Taiwan.
authors.forename: Shih-Ting
authors.initials: ST
authors.lastname: Tseng
authors.affiliation: 1] Department of Biotechnology, Hungkuang University, Taichung, Taiwan [2] Taiwan Advance Biopharm (TABP), Inc., Xizhi City, New Taipei City, Taiwan.
authors.forename: Chia Shin
authors.initials: CS
authors.lastname: Yang
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Lai
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Tzu-Ping
authors.initials: TP
authors.lastname: Ko
authors.affiliation: Department of Biotechnology, Hungkuang University, Taichung, Taiwan.
authors.forename: Yeh
authors.initials: Y
authors.lastname: Chen
mesh_terms: D039903:Actinobacteria / Q000201:enzymology; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000378:metabolism; D008024:Ligands; D008780:Methyltransferases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008024:Ligands; D050505:Mutant Proteins; C005045:3-hydroxykynurenine; D007737:Kynurenine; D008780:Methyltransferases