Structure of the antitumour enzyme L-methionine gamma-lyase from Pseudomonas putida at 1.8 A resolution.
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.
Kudou
Daizou
D
Department of Biofunctional Chemistry, Graduate School of Natural Science and Technology, Okayama University, Okayama-Shi, Okayama, Japan.
Misaki
Shintaro
S
Yamashita
Masao
M
Tamura
Takashi
T
Takakura
Tomoaki
T
Yoshioka
Takayuki
T
Yagi
Shigeo
S
Hoffman
Robert M
RM
Takimoto
Akio
A
Esaki
Nobuyoshi
N
Inagaki
Kenji
K
D000595:Amino Acid Sequence; D001665:Binding Sites; D013437:Carbon-Sulfur Lyases / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016958:Pseudomonas putida / Q000201:enzymology*; D016415:Sequence Alignment
D013437:Carbon-Sulfur Lyases; C021558:L-methionine gamma-lyase