Structural basis for substrate specificity of l‐methionine decarboxylase

• Published in: Protein science 2021-03, Vol.30 (3), p.663-677
• Main Authors: Okawa, Atsushi, Shiba, Tomoo, Hayashi, Masaya, Onoue, Yuki, Murota, Masaki, Sato, Dan, Inagaki, Junko, Tamura, Takashi, Harada, Shigeharu, Inagaki, Kenji
• Format: Article
• Language: English
• Subjects: amino acid; amino acid decarboxylase; Amino acids; Amino Acids - chemistry; Amino Acids - genetics; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Carbon dioxide; Carboxy-Lyases - chemistry; Carboxy-Lyases - genetics; Carboxy-Lyases - metabolism; Catalysts; Catalytic Domain - genetics; Crystal structure; Decarboxylation; Free form; Full‐Length Papers; Intermediates; l ‐methionine decarboxylase; Methionine; Methionine decarboxylase; Models, Molecular; Mutagenesis, Site-Directed; Protonation; pyridoxal 5′‐phosphate; Reaction intermediates; reaction mechanism; Residues; site‐directed mutagenesis; Streptomyces; Streptomyces - enzymology; Streptomyces - genetics; Substrate specificity; Substrate Specificity - genetics; Substrates; Vitamin B6; vitamin B6 ‐ dependent enzyme
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1002/pro.4027

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.