The Biosynthesis of Heterophyllin B in Pseudostellaria heterophylla From prePhHB-Encoded Precursor

Zheng, Wei; Zhou, Tao; Li, Jun; Jiang, Wei-Ke; Zhang, Jinqiang; Xiao, Chao; Wei, Dequn; Yang, Chun-Lin; Xu, Rui; Gong, Anhui; Zhang, Chen; Bi, Yan

doi:10.3389/fpls.2019.01259

Cited by 11 publications

(6 citation statements)

References 42 publications

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“…6C). Among them, only ZcAEP1 is a full-length sequence with a typical architecture of AEPs, including a signal peptide (residue 1-22), an N-terminal domain (residue [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38], a catalytic core domain (residue 39-321), a linker (residue 322-340), and a C-terminal cap domain (residue 341-481). ZcAEP2 has only 10 different residues compared to ZcAEP1, but it lacks ~50 residues at its Nterminus.…”

Section: Identification Of Aep-type Peptide Ligase From the Monocot P...mentioning

confidence: 99%

Development of a general bioluminescent activity assay for peptide ligases

et al. 2022

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In recent years, some peptide ligases have been identified, such as bacterial sortases and certain plant asparaginyl or prolyl endopeptidases. Peptide ligases have wide applications in protein labelling and cyclic peptide synthesis. To characterize various known peptide ligases or identify new ones, we propose a general bioluminescent activity assay via the genetic fusion of a recognition motif of peptide ligase(s) to the C‐terminus of an inactive large NanoLuc fragment (LgBiT) and the chemical introduction of a nucleophilic motif preferred by the peptide ligase(s) to the N‐terminus of the low‐affinity SmBiT complementation tag. After the inactive ligation version LgBiT protein was ligated with the low‐affinity ligation version SmBiT tag by the expected peptide ligase(s), its luciferase activity would be restored and could be quantified sensitively according to the measured bioluminescence. In the present study, we first validated the bioluminescent activity assay using bacterial sortase A and plant‐derived butelase‐1. Subsequently, we screened novel peptide ligases from crude extracts of selected plants using two LgBiT‐SmBiT ligation pairs. Among 80 common higher plants, we identified that five of them likely express asparaginyl endopeptidase‐type peptide ligase and four of them likely express prolyl endopeptidase‐type peptide ligase, suggesting that peptide ligases are not so rare in higher plants and more of them await discovery. The present bioluminescent activity assay is ultrasensitive, convenient for use, and resistant to protease interference, and thus would have wide applications for characterizing known peptide ligases or screening new ones from various sources in future studies.

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Section: Identification Of Aep-type Peptide Ligase From the Monocot P...mentioning

confidence: 99%

Development of a general bioluminescent activity assay for peptide ligases

et al. 2022

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“…Heterophyllin B (HB) is the most famous and most studied cyclopeptide in P. heterophylla. "IFGGLPPP" is a linear peptide precursor of Heterophyllin B proposed by W Zheng et al [51]. In our previous docking study of DPP4, the discussion covered HB's linear precursor IFGGLPPP and a series of its derivatives.…”

Section: Exploring the Possibility Of Hb Linear Precursor "Ifgglppp" ...mentioning

confidence: 99%

Investigating Potential GLP-1 Receptor Agonists in Cyclopeptides from Pseudostellaria heterophylla, Linum usitatissimum, and Drymaria diandra, and Peptides Derived from Heterophyllin B for the Treatment of Type 2 Diabetes: An In Silico Study

Liao

Tzen

2022

Metabolites

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GLP-1 receptor agonists stimulate GLP-1R to promote insulin secretion, whereas DPP4 inhibitors slow GLP-1 degradation. Both approaches are incretin-based therapies for T2D. In addition to GLP-1 analogs, small nonpeptide GLP-1RAs such as LY3502970, TT-OAD2, and PF-06882961 have been considered as possible therapeutic alternatives. Pseudostellaria heterophylla, Linum usitatissimum, and Drymaria diandra are plants rich in cyclopeptides with hypoglycemic effects. Our previous study demonstrated the potential of their cyclopeptides for DPP4 inhibition. Reports of cyclic setmelanotide as an MC4R (GPCR) agonist and cyclic α-conotoxin chimeras as GLP-1RAs led to docking studies of these cyclopeptides with GLP-1R. Heterophyllin B, Pseudostellarin B, Cyclolinopeptide B, Cyclolinopeptide C, Drymarin A, and Diandrine C are abundant in these plants, with binding affinities of −9.5, −10.4, −10.3, −10.6, −11.2, and −11.9 kcal/mol, respectively. The configuration they demonstrated established multiple hydrogen bonds with the transmembrane region of GLP-1R. DdC:(cyclo)-GGPYWP showed the most promising docking score. The results suggest that, in addition to DPP4, GLP-1R may be a hypoglycemic target of these cyclopeptides. This may bring about more discussion of plant cyclopeptides as GLP-1RAs. Moreover, peptides derived from the HB precursor (IFGGLPPP), including IFGGWPPP, IFPGWPPP, IFGGYWPPP, and IFGYGWPPPP, exhibited diverse interactions with GLP-1R and displayed backbones available for further research.

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“…The copyright holder for this this version posted November 2, 2021. ; https://doi.org/10.1101/2021.11.01.466836 doi: bioRxiv preprint from Saponaria vaccaria and Pseudostellaria heterophylla contain a proline residue at the C-terminus of their mature peptide [33,34]. According to their amino acid sequence, we designed a possible ligation pair for screening PEP-type peptide ligase from the crude extract of some plants.…”

Section: Screening Possible Pep-type Peptide Ligase From Crude Extract Of Some Plantsmentioning

confidence: 99%

Development of a novel bioluminescent activity assay for peptide ligases

Zhang

Shao

Wang

et al. 2021

Preprint

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In recent years, some peptide ligases have been identified, such as bacterial sortases and certain plant asparaginyl or prolyl endopeptidases. Peptide ligases have wide applications in protein labeling and cyclic peptide synthesis. To characterize known peptide ligases or identify new ones, we propose a novel bioluminescent activity assay via the genetic fusion of a recognition motif of a peptide ligase to the C-terminus of an inactive large NanoLuc fragment (LgBiT) and the chemical introduction of a nucleophilic motif preferred by the peptide ligase to the N-terminus of the low-affinity SmBiT complementation tag. When the inactive ligation version LgBiT protein was ligated with the low-affinity ligation version SmBiT tag by the expected peptide ligase, its luciferase activity would be restored and could be quantified sensitively according to the measured bioluminescence. In the present study, we first validated the novel bioluminescent activity assay using bacterial sortase A and plant butelase-1. Subsequently, we screened novel peptide ligases from crude extracts of selected plants using two LgBiT–SmBiT ligation pairs. Among 80 common higher plants, we identified that five of them likely express asparaginyl endopeptidase-type peptide ligase and four of them likely express prolyl endopeptidase-type peptide ligase, suggesting that peptide ligases are not so rare in higher plants and more of them await discovery. The novel bioluminescent activity assay is ultrasensitive, convenient for use, and resistant to protease interference, and thus would have wide applications for characterizing known peptide ligases or screening new ones from various sources in future studies.

show abstract

The Biosynthesis of Heterophyllin B in Pseudostellaria heterophylla From prePhHB-Encoded Precursor

Cited by 11 publications

References 42 publications

Development of a general bioluminescent activity assay for peptide ligases

Development of a general bioluminescent activity assay for peptide ligases

Investigating Potential GLP-1 Receptor Agonists in Cyclopeptides from Pseudostellaria heterophylla, Linum usitatissimum, and Drymaria diandra, and Peptides Derived from Heterophyllin B for the Treatment of Type 2 Diabetes: An In Silico Study

Development of a novel bioluminescent activity assay for peptide ligases

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