PCD_DCoH: The bifunctional protein pterin-4alpha-carbinolamine dehydratase (PCD), also known as DCoH (dimerization cofactor of hepatocyte nuclear factor-1), is both a transcription activator and a metabolic enzyme. DCoH stimulates gene expression by associating with specific DNA binding proteins such as HNF-1alpha (hepatocyte nuclear factor-1) and Xenopus enhancer of rudimentary homologue (XERH). DCoH also catalyzes the dehydration of 4alpha- hydroxy- tetrahydrobiopterin (4alpha-OH-BH4) to quinoiddihydrobiopterin, a percursor of the phenylalanine hydroxylase cofactor BH4 (tetrahydrobiopterin). The DCoH homodimer has a saddle-shaped structure similar to that of TBP (TATA binding protein). Two DCoH proteins have been identifed in humans: DCoH1 and DCoH2. Mutations in human DCoH1 cause hyperphenylalaninemia. Loss of enzymic activity of DCoH in humans is associated with the depigmentation disorder vitiligo. DCoH1 has been reported to be overexpessed in colon cancer carcinomas and in malignant melanomas.
Feature 1:substrate binding site [chemical binding site]
Evidence:
Comment:Each of the four substrate binding sites within the homotetramer is located adjacent to a saddle motif
Structure:1DCP_A; Rattus norvegicus DCoH, bound with the biopterin substrate analog, 7,8-dihydrobiopterin, contacts at 3.5 A. Structure 1DCP includes two homotetramers.
Jiyao W et al.(2023). "The conserved domain database in 2023.",