Novel hemoglobin-derived xanthine oxidase inhibitory peptides: Enzymatic preparation and inhibition mechanisms
Xanthine oxidase (XO) activity is critical to modulate uric acid and hyperuricemia. Hemoglobin was hydrolyzed by bromelain and the protease from Geobacillus stearothermophilus (GsProS8) to express excellent protein recovery rate (54.87%) and XO inhibitory activity (IC50 of 0.744 mg/mL), resulting fr...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-03-01
|
| Series: | Journal of Functional Foods |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464623000592 |
| _version_ | 1811155485109256192 |
|---|---|
| author | Peng Zhang Zhengqiang Jiang Jia Lei Qiaojuan Yan Chang Chang |
| author_facet | Peng Zhang Zhengqiang Jiang Jia Lei Qiaojuan Yan Chang Chang |
| author_sort | Peng Zhang |
| collection | DOAJ |
| description | Xanthine oxidase (XO) activity is critical to modulate uric acid and hyperuricemia. Hemoglobin was hydrolyzed by bromelain and the protease from Geobacillus stearothermophilus (GsProS8) to express excellent protein recovery rate (54.87%) and XO inhibitory activity (IC50 of 0.744 mg/mL), resulting from higher contents of tryptophan, glutamic acid and glycine. The hydrolysate was fractionated and identified three novel XO inhibitory peptides IVYPW, YPWTQ, and LITGLW (IC50 of 0.63–1.09 mM). Unlike allopurinol, IVYPW and YPWTQ were mixed-type inhibitors, whereas LITGLW was a non-competitive inhibitor. In addition to the well-recognized contribution of tryptophan, molecular docking studies revealed tyrosine residue in IVYPW and YPWTQ importantly enhanced XO inhibitory activities via hydrogen-bond and Pi-Sigma interactions with Thr1010 and His875, respectively. The total number of Pi-related interactions positively determined XO inhibition as comparing IVYPW, YPWTQ and LITGLW. This study provided a promising strategy to prepare anti-hyperuricemic peptides and understand inhibition mechanisms for the management of hyperuricemia. |
| first_indexed | 2024-04-10T04:35:06Z |
| format | Article |
| id | doaj.art-5654fa0dd30f48d2a2febaab757351b5 |
| institution | Directory Open Access Journal |
| issn | 1756-4646 |
| language | English |
| last_indexed | 2024-04-10T04:35:06Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Functional Foods |
| spelling | doaj.art-5654fa0dd30f48d2a2febaab757351b52023-03-10T04:34:36ZengElsevierJournal of Functional Foods1756-46462023-03-01102105459Novel hemoglobin-derived xanthine oxidase inhibitory peptides: Enzymatic preparation and inhibition mechanismsPeng Zhang0Zhengqiang Jiang1Jia Lei2Qiaojuan Yan3Chang Chang4College of Engineering, China Agricultural University, Beijing 100083, ChinaKey Laboratory of Food Bioengineering (China National Light Industry), College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, ChinaKey Laboratory of Food Bioengineering (China National Light Industry), College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, ChinaCollege of Engineering, China Agricultural University, Beijing 100083, ChinaKey Laboratory of Food Bioengineering (China National Light Industry), College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; Corresponding author at: College of Food Science and Nutritional Engineering, China Agricultural University 17 Qinghua Donglu, Beijing 100083, China.Xanthine oxidase (XO) activity is critical to modulate uric acid and hyperuricemia. Hemoglobin was hydrolyzed by bromelain and the protease from Geobacillus stearothermophilus (GsProS8) to express excellent protein recovery rate (54.87%) and XO inhibitory activity (IC50 of 0.744 mg/mL), resulting from higher contents of tryptophan, glutamic acid and glycine. The hydrolysate was fractionated and identified three novel XO inhibitory peptides IVYPW, YPWTQ, and LITGLW (IC50 of 0.63–1.09 mM). Unlike allopurinol, IVYPW and YPWTQ were mixed-type inhibitors, whereas LITGLW was a non-competitive inhibitor. In addition to the well-recognized contribution of tryptophan, molecular docking studies revealed tyrosine residue in IVYPW and YPWTQ importantly enhanced XO inhibitory activities via hydrogen-bond and Pi-Sigma interactions with Thr1010 and His875, respectively. The total number of Pi-related interactions positively determined XO inhibition as comparing IVYPW, YPWTQ and LITGLW. This study provided a promising strategy to prepare anti-hyperuricemic peptides and understand inhibition mechanisms for the management of hyperuricemia.http://www.sciencedirect.com/science/article/pii/S1756464623000592HemoglobinEnzymatic hydrolysisGeobacillus stearothermophilusXO inhibitory peptidesInhibition typeMolecular docking |
| spellingShingle | Peng Zhang Zhengqiang Jiang Jia Lei Qiaojuan Yan Chang Chang Novel hemoglobin-derived xanthine oxidase inhibitory peptides: Enzymatic preparation and inhibition mechanisms Journal of Functional Foods Hemoglobin Enzymatic hydrolysis Geobacillus stearothermophilus XO inhibitory peptides Inhibition type Molecular docking |
| title | Novel hemoglobin-derived xanthine oxidase inhibitory peptides: Enzymatic preparation and inhibition mechanisms |
| title_full | Novel hemoglobin-derived xanthine oxidase inhibitory peptides: Enzymatic preparation and inhibition mechanisms |
| title_fullStr | Novel hemoglobin-derived xanthine oxidase inhibitory peptides: Enzymatic preparation and inhibition mechanisms |
| title_full_unstemmed | Novel hemoglobin-derived xanthine oxidase inhibitory peptides: Enzymatic preparation and inhibition mechanisms |
| title_short | Novel hemoglobin-derived xanthine oxidase inhibitory peptides: Enzymatic preparation and inhibition mechanisms |
| title_sort | novel hemoglobin derived xanthine oxidase inhibitory peptides enzymatic preparation and inhibition mechanisms |
| topic | Hemoglobin Enzymatic hydrolysis Geobacillus stearothermophilus XO inhibitory peptides Inhibition type Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S1756464623000592 |
| work_keys_str_mv | AT pengzhang novelhemoglobinderivedxanthineoxidaseinhibitorypeptidesenzymaticpreparationandinhibitionmechanisms AT zhengqiangjiang novelhemoglobinderivedxanthineoxidaseinhibitorypeptidesenzymaticpreparationandinhibitionmechanisms AT jialei novelhemoglobinderivedxanthineoxidaseinhibitorypeptidesenzymaticpreparationandinhibitionmechanisms AT qiaojuanyan novelhemoglobinderivedxanthineoxidaseinhibitorypeptidesenzymaticpreparationandinhibitionmechanisms AT changchang novelhemoglobinderivedxanthineoxidaseinhibitorypeptidesenzymaticpreparationandinhibitionmechanisms |