Location of the Active Site and Proposed Catalytic Mechanism of Pterin-4A-Carbinolamine Dehydratase

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Location of the active site and proposed catalytic mechanism of pterin-4a-carbinolamine dehydratase.

Based on the recently solved three-dimensional structure of pterin-4a-carbinolamine dehydratase from rat/human liver the involvement of the proposed active-site residues Glu57, Asp60, His61, His62, Tyr69, His79, Arg87 and Asp88 was examined by site-directed mutagenesis. Most of the mutants showed reduced activity, and only the Glu57-->Ala mutant and the His61-->Ala, His62-->Ala double mutant we...

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Pterin-4a-carbinolamine dehydratase from Pseudomonas aeruginosa: characterization, catalytic mechanism and comparison to the human enzyme.

The three-dimensional structure of pterin-4a-carbinolamine dehydratase (PCD) from Pseudomonas aeruginosa has been solved. Based on this we have investigated the roles of putative active center residues through functional replacement by site-directed mutagenesis. Three histidines, His73, His74 and His91, appear to be involved in dehydration catalysis. The three-dimensional positions of these res...

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Phylogenomic and functional analysis of pterin-4a-carbinolamine dehydratase family (COG2154) proteins in plants and microorganisms.

Pterin-4a-carbinolamine dehydratases (PCDs) recycle oxidized pterin cofactors generated by aromatic amino acid hydroxylases (AAHs). PCDs are known biochemically only from animals and one bacterium, but PCD-like proteins (COG2154 in the Clusters of Orthologous Groups [COGs] database) are encoded by many plant and microbial genomes. Because these genomes often encode no AAH homologs, the annotati...

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On the Mechanism of Pterin-4a-carbinolamine Dehydratase - Synthesis of New Substrate Analogues and Interaction with the Enzyme

Introduction Pterin-4a-carbinolamine dehydratase (PCD) is a bifunctional mamnlalian enzyme that acts, on the one hand, as dimerization cofactor of the hepatocyte nuclear factor 1-a. (1). On the other hand it takes part in the metabolism of tetrahydrobiopterin, the natural cofactor of the aromatic amino acid hydroxylases. PCD catalyzes the dehydration of 4a-OH-tetrahydrobiopterin (carbinolamine)...

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7-substituted pterins in humans with suspected pterin-4a-carbinolamine dehydratase deficiency. Mechanism of formation via non-enzymatic transformation from 6-substituted pterins.

A recently described new form of hyperphenylalaninemia is characterized by the excretion of 7-substituted isomers of biopterin and neopterin and 7-oxo-biopterin in the urine of patients. It has been shown that the 7-substituted isomers of biopterin and neopterin derive from L-tetrahydrobiopterin and D-tetrahydroneopterin and are formed during hydroxylation of phenylalanine to tyrosine with rat ...

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ژورنال

عنوان ژورنال: European Journal of Biochemistry

سال: 1996

ISSN: 0014-2956,1432-1033

DOI: 10.1111/j.1432-1033.1996.00858.x