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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.

SUBMITTER: Chen SC

PROVIDER: S-EPMC4426599 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Structure and mechanism of an antibiotics-synthesizing 3-hydroxykynurenine C-methyltransferase.

Chen Sheng-Chia SC Huang Chi-Hung CH Lai Shu-Jung SJ Liu Jai-Shin JS Fu Pin-Kuei PK Tseng Shih-Ting ST Yang Chia Shin CS Lai Mei-Chin MC Ko Tzu-Ping TP Chen Yeh Y

Scientific reports 20150511

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 resu ...[more]

PMID: 25960001

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