OSAKA, Japan—Investigators from the Institute of Scientific and Industrial Research at Osaka University, together with the Hiroshima Institute of Technology, have announced the discovery of a new protein which allows an organism to conduct an initial, essential step in converting amino acid residues on a crosslinked polypeptide into an enzyme cofactor.
Researchers discover new protein
Researchers have identified the protein that converts amino acids into the enzyme cofactor cysteine tryptophylquinone| 2 min read
DDNews Staff
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OSAKA, Japan—Investigators from the Institute of Scientific and Industrial Research at Osaka University, together with the Hiroshima Institute of Technology, have announced the discovery of a new protein which allows an organism to conduct an initial, essential step in converting amino acid residues on a crosslinked polypeptide into an enzyme cofactor.
The study, entitled “Functional and structural characterization of a flavoprotein monooxygenase essential for biogenesis of tryptophylquinone cofactor,” has been published in Nature Communications. This research has the potential to lead to a better understanding of the biochemistry underlying catalysis in cells.
The rates of these reactions are controlled by enzymes, which catalyze specific processes that would otherwise take much longer. A number of enzymes require specialized molecules called cofactors, which can help shuttle electrons back and forth during oxidation-reduction reactions. But these cofactors themselves must be produced by the organisms, and often require the assistance of previously existing proteins.
Osaka University scientists have identified a novel protein, called QhpG, that is essential for the biogenesis of the enzyme cofactor cysteine tryptophylquinone (CTQ). By analyzing the mass of the reaction products and determining its crystal structure, the researchers were able to deduce the catalytic function of QhpG — which is adding two hydroxyl groups to a specific tryptophan residue within an active-site subunit QhpC of quinoheme protein amine dehydrogenase, the bacterial enzyme catalyzing the oxidation of various primary amines. The resulting dihydroxylated tryptophan and an adjacent cysteine residue are then converted to cofactor CTQ.
The action of QhpG is somewhat unusual, compared with other protein-modifying enzymes. It reacts with the tryptophan residue on the QhC triply crosslinked by another enzyme QhpD. Tryptophan — which naturally contains rings with conjugated bonds — needs the fewest changes to become a quinone cofactor.
“Although several enzymes are known to contain a quinone cofactor derived from a tryptophan residue, the mechanism involved in post-translational modification, as well as the structures of the enzymes involved in their biogenesis, remains poorly understood,” said Toshinori Oozeki, lead author of the study.
The proteins were obtained by introducing plasmids with the corresponding genes into E. coli bacteria, and made into crystals. X-ray diffraction of the crystal determined the QhpG protein structure. The team then used computer software to simulate the docking of the target molecules — the triply crosslinked polypeptide QhpC — based on the crystal structure they found for QhpG. The two post-translational modifications of QhpC are successively carried out in the modification enzyme complex QhpD-QhpG.
“Our findings can be applied to development of novel bioactive peptides using enzymes that modify amino acids,” noted Toshihide Okajima, senior author of the study.
