Crystal structure of the pyridoxal-5'-phosphate-dependent serine dehydratase from human liver.
L-serine dehydratase (SDH), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and L-threonine to yield pyruvate or 2-oxobutyrate. The crystal structure of L-serine dehydratase from human liver (hSDH) has been solved at 2.5 A-resolution by molecular replacement. The structure is a homodimer and reveals a fold typical for beta-family PLP-dependent enzymes. Each monomer serves as an active unit and is subdivided into two distinct domains: a small domain and a PLP-binding domain that covalently anchors the cofactor. Both domains show the typical open alpha/beta architecture of PLP enzymes. Comparison with the rSDH-(PLP-OMS) holo-enzyme reveals a large structural difference in active sites caused by the artifical O-methylserine. Furthermore, the activity of hSDH-PLP was assayed and it proved to show catalytic activity. That suggests that the structure of hSDH-PLP is the first structure of the active natural holo-SDH.
Sun
Lei
L
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China.
Bartlam
Mark
M
Liu
Yiwei
Y
Pang
Hai
H
Rao
Zihe
Z
D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D019281:Dimerization; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D006801:Humans; D006860:Hydrogen Bonding; D012695:L-Serine Dehydratase / Q000737:chemistry* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011732:Pyridoxal Phosphate / Q000378:metabolism*; D051381:Rats; D016415:Sequence Alignment; D014867:Water / Q000378:metabolism
D014867:Water; D011732:Pyridoxal Phosphate; D012695:L-Serine Dehydratase