R. Ficner et al., 3-DIMENSIONAL STRUCTURE OF THE BIFUNCTIONAL PROTEIN PCD DCOH, A CYTOPLASMIC ENZYME INTERACTING WITH TRANSCRIPTION FACTOR HNF1/, EMBO journal, 14(9), 1995, pp. 2034-2042
The bifunctional protein pterin-4a-carbinolamine dehydratase (PCD)/dim
erization cofactor of HNF1 (DCoH) is a cytoplasmic enzyme involved in
the tetrahydrobiopterin regeneration and is found in complex with the
transcription factor HNF1 in liver cell nuclei, An atypical hyperpheny
lalaninemia and the depigmentation disorder vitiligo are related to a
deficiency of PCD/DCoH activity, The crystal structure of PCD/DCoH was
solved by multiple isomorphous replacement and refined to a crystallo
graphic R-factor of 20.5% at 2.7 Angstrom resolution, The single domai
n monomer comprises three alpha-helices packed against one side of a f
our-stranded, antiparallel beta-sheet, The functional enzyme is a homo
-tetramer of 222 symmetry where each of the monomers contributes one h
elix to a central four helix bundle, In the tetramer two monomers form
an eight-stranded, antiparallel beta-sheet with six helices packing a
gainst it from one side. The concave, hydrophobic surface of the eight
-stranded beta-sheet with its two protruding loops at either end is re
miniscent of the saddle-like shape seen in the TATA-box binding protei
n, PCD/DCoH binds as a dimer to the helical dimerization domain of dim
eric HNF1 forming a hetero-tetramer possibly through a mixed four heli
x bundle.