Structure of the antitumour enzyme L-methionine gamma-lyase from Pseudomonas putida at 1.8 A resolution
Autor: | Masao Yamashita, Daizou Kudou, Akio Takimoto, Takashi Tamura, Shigeo Yagi, Takayuki Yoshioka, Tomoaki Takakura, Nobuyoshi Esaki, Robert M. Hoffman, Shintaro Misaki, Kenji Inagaki |
---|---|
Rok vydání: | 2007 |
Předmět: |
Models
Molecular Stereochemistry Protein subunit Molecular Sequence Data Crystallography X-Ray Biochemistry chemistry.chemical_compound Amino Acid Sequence Molecular Biology chemistry.chemical_classification Methionine Binding Sites biology Pseudomonas putida Active site Substrate (chemistry) General Medicine biology.organism_classification Lyase Protein Structure Tertiary Carbon-Sulfur Lyases Enzyme Monomer chemistry biology.protein Dimerization Sequence Alignment |
Zdroj: | Journal of biochemistry. 141(4) |
ISSN: | 0021-924X |
Popis: | l-Methionine gamma-lyase (EC 4.4.1.11, MGL_Pp) from Pseudomonas putida is a multifunctional enzyme, which belongs to the gamma-family of pyridoxal-5'-phosphate (PLP) dependent enzymes. In this report, we demonstrate that the three-dimensional structure of MGL_Pp has been completely solved by the molecular replacement method to an R-factor of 20.4% at 1.8 A resolution. Detailed information of the overall structure of MGL_Pp supplies a clear picture of the substrate- and PLP-binding pockets. Tyr59 and Arg61 of neighbouring subunits, which are strongly conserved in other gamma-family enzymes, contact the phosphate group of PLP. These residues are important as the main anchor within the active site. Lys240, Asp241 and Arg61 of one partner monomer and Tyr114 and Cys116 of the other partner monomer form a hydrogen-bond network in the MGL active site which is specific for MGLs. It is also suggested that electrostatic interactions at the subunit interface are involved in the stabilization of the structural conformation. The detailed structure will facilitate the development of MGL_Pp as an anticancer drug. |
Databáze: | OpenAIRE |
Externí odkaz: |