Crystal structure of human pyridoxal kinase.
Pyridoxal kinase, a member of the ribokinase superfamily, catalyzes the ATP-dependent phosphorylation reaction of vitamin B6 and is an essential enzyme in the formation of pyridoxal-5'-phosphate, a key cofactor for over 100 enzymes. Pyridoxal kinase is thus regarded as a potential target for pharmacological agents. In this paper, we report the 2.8 angstroms crystal structure of human pyridoxal kinase (HPLK) expressed in Escherichia coli. The diffraction data revealed unexpected merohedral perfect twinning along the crystallographic c axis. Taking perfect twinning into account, the structure in dimeric form was well refined according to the CNS program. Structure comparison reveals that the key 12-residue peptide over the active site in HPLK is a beta-strand/loop/beta-strand flap, while the corresponding peptide in sheep brain enzyme adopts a loop conformation. Moreover, HPLK possesses a more hydrophobic ATP-binding pocket. This structure will facilitate further biochemical studies and structure-based design of drugs related to pyridoxal kinase.
Cao
Peng
P
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Gong
Yong
Y
Tang
Lin
L
Leung
Yun-Chung
YC
Jiang
Tao
T
D000255:Adenosine Triphosphate / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D018360:Crystallography, X-Ray / Q000379:methods*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D017433:Protein Structure, Secondary; D011731:Pyridoxal Kinase / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012756:Sheep
D000255:Adenosine Triphosphate; D011731:Pyridoxal Kinase