Crystal structure of DCoH, a bifunctional, protein-binding transcriptional coactivator.
DCoH, the dimerization cofactor of hepatocyte nuclear factor-1, stimulates gene expression by associating with specific DNA binding proteins and also catalyzes the dehydration of the biopterin cofactor of phenylalanine hydroxylase. The x-ray crystal structure determined at 3 angstrom resolution reveals that DCoH forms a tetramer containing two saddle-shaped grooves that comprise likely macromolecule binding sites. Two equivalent enzyme active sites flank each saddle, suggesting that there is a spatial connection between the catalytic and binding activities. Structural similarities between the DCoH fold and nucleic acid-binding proteins argue that the saddle motif has evolved to bind diverse ligands or that DCoH unexpectedly may bind nucleic acids.
Endrizzi
J A
JA
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3206, USA.
Cronk
J D
JD
Wang
W
W
Crabtree
G R
GR
Alber
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D005786:Gene Expression Regulation; D006836:Hydro-Lyases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D006836:Hydro-Lyases; C076392:pterin-4a-carbinolamine dehydratase