Cao Peng, Gong Yong, Tang Lin, Leung Yun-Chung, Jiang Tao
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
J Struct Biol. 2006 Jun;154(3):327-32. doi: 10.1016/j.jsb.2006.02.008. Epub 2006 Mar 20.
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.
吡哆醛激酶是核糖激酶超家族的成员之一，催化维生素B6的ATP依赖性磷酸化反应，是形成磷酸吡哆醛（一种100多种酶的关键辅因子）过程中的一种必需酶。因此，吡哆醛激酶被视为药物的潜在靶点。在本文中，我们报道了在大肠杆菌中表达的人源吡哆醛激酶（HPLK）的2.8埃晶体结构。衍射数据显示沿晶体学c轴存在意想不到的半面体完全孪晶。考虑到完全孪晶，根据CNS程序对二聚体形式的结构进行了很好的精修。结构比较表明，HPLK活性位点上关键的12个残基肽是一个β-链/环/β-链瓣，而羊脑酶中的相应肽采用环构象。此外，HPLK具有一个更疏水的ATP结合口袋。该结构将有助于进一步开展与吡哆醛激酶相关的生化研究和基于结构的药物设计。
