The crystal structure of augmenter of liver regeneration: A mammalian FAD-dependent sulfhydryl oxidase.
The crystal structure of recombinant rat augmenter of liver regeneration (ALRp) has been determined to 1.8 A. The protein is a homodimer, stabilized by extensive noncovalent interactions and a network of hydrogen bonds, and possesses a noncovalently bound FAD in a motif previously found only in the related protein ERV2p. ALRp functions in vitro as a disulfide oxidase using dithiothreitol as reductant. Reduction of the flavin by DTT occurs under aerobic conditions resulting in a spectrum characteristic of a neutral semiquinone. This semiquinone is stable and is only fully reduced by addition of dithionite. Mutation of either of two cysteine residues that are located adjacent to the FAD results in inactivation of the oxidase activity. A comparison of ALRp with ERV2p is made that reveals a number of significant structural differences, which are related to the in vivo functions of these two proteins. Possible physiological roles of ALR are examined and a hypothesis that it may serve multiple roles is proposed.
Wu
Chia-Kuei
CK
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, USA.
Dailey
Tamara A
TA
Dailey
Harry A
HA
Wang
Bi-Cheng
BC
Rose
John P
JP
D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D003545:Cysteine; D004229:Dithiothreitol; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D050862:Oxidoreductases Acting on Sulfur Group Donors
D003545:Cysteine; D004229:Dithiothreitol; D005182:Flavin-Adenine Dinucleotide; D010088:Oxidoreductases; D011506:Proteins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C088825:GFER protein, rat