Structural basis for substrate specificity of l‐methionine decarboxylase |
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| Authors: | Atsushi Okawa Tomoo Shiba Masaya Hayashi Yuki Onoue Masaki Murota Dan Sato Junko Inagaki Takashi Tamura Shigeharu Harada Kenji Inagaki |
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| Affiliation: | 1. Department of Biofunctional Chemistry, Okayama University, Okayama Japan ; 2. Department of Applied Biology, Kyoto Institute of Technology, Kyoto Japan ; 3. The Center for Advanced Insect Research Promotion (CAIRP), Kyoto Institute of Technology, Kyoto Japan ; 4. Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama Japan |
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| Abstract: | l ‐Methionine decarboxylase (MetDC) from Streptomyces sp. 590 is a vitamin B6‐dependent enzyme and catalyzes the non‐oxidative decarboxylation of l ‐methionine to produce 3‐methylthiopropylamine and carbon dioxide. We present here the crystal structures of the ligand‐free form of MetDC and of several enzymatic reaction intermediates. Group II amino acid decarboxylases have many residues in common around the active site but the residues surrounding the side chain of the substrate differ. Based on information obtained from the crystal structure, and mutational and biochemical experiments, we propose a key role for Gln64 in determining the substrate specificity of MetDC, and for Tyr421 as the acid catalyst that participates in protonation after the decarboxylation reaction. |
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| Keywords: | amino acid, amino acid decarboxylase, crystal structure, l‐ methionine decarboxylase, pyridoxal 5′ ‐ phosphate, reaction mechanism, site‐ directed mutagenesis, Streptomyces, substrate specificity, vitamin B6 ‐ dependent enzyme |
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