Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 Å Resolution

نویسندگان

  • Alireza Nematollahi
  • Guanchen Sun
  • Stephen J. Harrop
  • Jane R. Hanrahan
  • W. Bret Church
چکیده

Kynurenine aminotransferase II (KAT-II) is a 47 kDa pyridoxal phosphate (PLP)-dependent enzyme, active as a homodimer, which catalyses the transamination of the amino acids kynurenine (KYN) and 3-hydroxykynurenine (3-HK) in the tryptophan pathway, and is responsible for producing metabolites that lead to kynurenic acid (KYNA), which is implicated in several neurological diseases such as schizophrenia. In order to fully describe the role of KAT-II in the pathobiology of schizophrenia and other brain disorders, the crystal structure of full-length PLP-form hKAT-II was determined at 1.83 Å resolution, the highest available. The electron density of the active site reveals an aldimine linkage between PLP and Lys263, as well as the active site residues, which characterize the fold-type I PLP-dependent enzymes.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Crystal structure of human kynurenine aminotransferase II, a drug target for the treatment of schizophrenia.

Kynurenic acid is an endogenous neuroactive compound whose unbalancing is involved in the pathogenesis and progression of several neurological diseases. Kynurenic acid synthesis in the human brain is sustained by the catalytic activity of two kynurenine aminotransferases, hKAT I and hKAT II. A wealth of pharmacological data highlight hKAT II as a sensible target for the treatment of neuropathol...

متن کامل

Kynurenine Aminotransferase Isozyme Inhibitors: A Review

Kynurenine aminotransferase isozymes (KATs 1-4) are members of the pyridoxal-5'-phosphate (PLP)-dependent enzyme family, which catalyse the permanent conversion of l-kynurenine (l-KYN) to kynurenic acid (KYNA), a known neuroactive agent. As KATs are found in the mammalian brain and have key roles in the kynurenine pathway, involved in different categories of central nervous system (CNS) disease...

متن کامل

Solid–Solid Synthesis, Crystal Structure and Thermal Decomposition of Copper(II) Complex of 2-Picolinic Acid

The copper(II) complex [Cu(pic)2]·2H2O was synthesized with 2-picolinic acid (Hpic) and copper acetate as reactants by room temperature solid-solid reaction. The composition and structure of the complex was characterized by elemental analyses, single crystal X-ray diffraction, X-ray powder diffraction, FT-IR spectroscopy and thermogravimetry-differential scanning calor...

متن کامل

Synthesis, Characterization and Catalytic Study of a Novel Binuclear Paddle-wheel Palladium(II) Complex in the Mizoroki-Heck Reaction

A new binuclear paddle-wheel palladium(II) complex of [Pd2(μ-mtzt)4]dmgH2 (1) has been prepared by the treatment of PdCl2 in acetonitrile with mixture of 1-methyl-1H-1,2,3,4-tetrazole-5-thiol (Hmtzt) and dimethylglyoxime (dmgH2) in methanol. Resulted complex was characterized by elemental analysis (CHNS), IR, UV–Vis absorption, 1H NMR spectroscopy and its structure was determined with single-cr...

متن کامل

Characteristic Features of Kynurenine Aminotransferase Allosterically Regulated by (Alpha)-Ketoglutarate in Cooperation with Kynurenine

Kynurenine aminotransferase from Pyrococcus horikoshii OT3 (PhKAT), which is a homodimeric protein, catalyzes the conversion of kynurenine (KYN) to kynurenic acid (KYNA). We analyzed the transaminase reaction mechanisms of this protein with pyridoxal-5'-phosphate (PLP), KYN and α-ketoglutaric acid (2OG) or oxaloacetic acid (OXA). 2OG significantly inhibited KAT activities in kinetic analyses, s...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 17  شماره 

صفحات  -

تاریخ انتشار 2016