51-35-4Relevant articles and documents
Recharacterization of the mammalian cytosolic type 2 (R)-β-hydroxybutyrate dehydrogenase as 4-oxo-L-proline reductase (EC 1.1.1.104)
Bozko, Maria,Drozak, Jakub,Jagielski, Adam K.,Kocdemir, Kubra,Kwiatkowski, Sebastian,Witecka, Apolonia,Zarod, Michal
, (2022/03/23)
Early studies revealed that chicken embryos incubated with a rare analog of L-proline, 4-oxo-L-proline, showed increased levels of the metabolite 4-hydroxy-L-proline. In 1962, 4-oxo-L-proline reductase, an enzyme responsible for the reduction of 4-oxo-L-proline, was partially purified from rabbit kidneys and characterized biochemically. However, only recently was the molecular identity of this enzyme solved. Here, we report the purification from rat kidneys, identification, and biochemical characterization of 4-oxo-L-proline reductase. Following mass spectrometry analysis of the purified protein preparation, the previously annotated mammalian cytosolic type 2 (R)-βhydroxybutyrate dehydrogenase (BDH2) emerged as the only candidate for the reductase. We subsequently expressed rat and human BDH2 in Escherichia coli, then purified it, and showed that it catalyzed the reversible reduction of 4-oxo-L-proline to cis-4-hydroxy-L-proline via chromatographic and tandem mass spectrometry analysis. Specificity studies with an array of compounds carried out on both enzymes showed that 4-oxo-L-proline was the best substrate, and the human enzyme acted with 12,500-fold higher catalytic efficiency on 4-oxo-L-proline than on (R)-β-hydroxybutyrate. In addition, human embryonic kidney 293T (HEK293T) cells efficiently metabolized 4-oxo-L-proline to cis-4-hydroxy-L-proline, whereas HEK293T BDH2 KO cells were incapable of producing cis-4-hydroxy-L-proline. Both WT and KO HEK293T cells also produced trans-4-hydroxy-L-proline in the presence of 4-oxo-L-proline, suggesting that the latter compound might interfere with the trans-4-hydroxy-L-proline breakdown in human cells. We conclude that BDH2 is a mammalian 4-oxo-L-proline reductase that converts 4-oxo-L-proline to cis-4-hydroxy-L-proline and not to trans-4-hydroxy-L-proline, as originally thought. We also hypothesize that this enzyme may be a potential source of cis-4-hydroxy-L-proline in mammalian tissues.
Studies on the selectivity of proline hydroxylases reveal new substrates including bicycles
Smart, Tristan J.,Hamed, Refaat B.,Claridge, Timothy D.W.,Schofield, Christopher J.
supporting information, (2019/11/26)
Studies on the substrate selectivity of recombinant ferrous-iron- and 2-oxoglutarate-dependent proline hydroxylases (PHs) reveal that they can catalyse the production of dihydroxylated 5-, 6-, and 7-membered ring products, and can accept bicyclic substrates. Ring-substituted substrate analogues (such hydroxylated and fluorinated prolines) are accepted in some cases. The results highlight the considerable, as yet largely untapped, potential for amino acid hydroxylases and other 2OG oxygenases in biocatalysis.
Peptide Tyrosinase Activators
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, (2015/06/10)
Peptides that increase melanin synthesis are provided. These peptides include pentapeptides YSSWY, YRSRK, and their variants. The peptides may activate the enzymatic activity of tyrosinase to increase melanin synthesis. The pharmaceutical, cosmetic, and other compositions including the peptides are also provided. The methods of increasing melanin production in epidermis of a subject are provided where the methods include administering compositions comprising an amount of one or more peptides effective to increase the melanin production. The methods also include treating vitiligo or other hypopigmentation disorders with compositions including one or more peptides.
