Abstract
In this work, we aim to combine bioinformatic prediction with a special experiment to search xanthine oxidase (XOD) inhibitory peptides from myosin of Pacific bluefin tuna (Thunnus Orientalis). The program Peptide Cutter, Peptide Ranker, Peptide Property calculator, Toxin Pred, and Discovery Studio (DS) help us screen the probable sequence. The result indicated that peptide ICRK has the highest inhibition effect and the value of IC50 was 14.18 mg/mL. The IC50 of the other two peptides (FDAK and MMER) were 16.8mg/mL and 15.3 mg/mL respectively. Molecular simulation demonstrated that ICRK interacted with amino acid residues GLU802, PHE914, ALA1079, GLU1261, LYS771, LEU648, THR1010, VAL1011 and SER 876. The possible inhibition mechanism of peptides and enzyme was stated by DS. Peptide ICRK blocked the entrance to the hydrophobic channel and stopped xanthine going into the active site of XOD. MMER and FDAK have the similar mechanism with ICRK. Therefore, ICRK, FDAK and MMER can be considered as nature XOD inhibitory peptides and further utilized.
Highlights
Gout is regarded as a metabolic disease, which leads deposition of urate in the joints and acute bouts of painful inflammatory arthritis
Xanthine oxidase (XOD) is an enzyme with low specificity, which can catalyze the formation of xanthine and uric acid from hypoxanthine, and directly catalyze the formation of uric acid from xanthine[2]
In the virtual simulation experiment, a total of 240 XOD inhibitory peptides were generated from tripeptides to nonapeptides, including eighty one tripeptides, forty eight tetrapeptides, thirty three pentapeptides, thirty five hexapeptides, twenty one heptapeptides, tenoctapeptides and twelve nonapeptides
Summary
Gout is regarded as a metabolic disease, which leads deposition of urate in the joints and acute bouts of painful inflammatory arthritis. High level of serum uric acid over a long period can cause the symptoms of gout[1]. Inhibition the activity of XOD could decrease the content of uric acid in vivo and relieve the symptoms of gout. Clinic drug allopurinol can effectively control serum uric acid level and has been used extensively. Allopurinol, an analog of purine, is a kind of noncompetitive inhibitor of XOD3. Allopurinol could lead hypersensitivity syndrome, impaired liver function, and renal toxicity with some patients 4. It is necessary for us to search for valid and nontoxic XOD inhibitors
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