A different perspective for nonphotochemical quenching in plant antenna complexes

Light-harvesting complexes of plants exert a dual function of light-harvesting (LH) and photoprotection through processes collectively called nonphotochemical quenching (NPQ). While LH processes are relatively well characterized, those involved in NPQ are less understood. Here, we characterize the quenching mechanisms of CP29, a minor LHC of plants, through the integration of two complementary enhanced-sampling techniques, dimensionality reduction schemes, electronic calculations and the analysis of cryo-EM data in the light of the predicted conformational ensemble. Our study reveals that the switch between LH and quenching state is more complex than previously thought. Several conformations of the lumenal side of the protein occur and differently affect the pigments’ relative geometries and interactions. Moreover, we show that a quenching mechanism localized on a single chlorophyll-carotenoid pair is not sufficient but many chlorophylls are simultaneously involved. In such a diffuse mechanism, short-range interactions between each carotenoid and different chlorophylls combined with a protein-mediated tuning of the carotenoid excitation energies have to be considered in addition to the commonly suggested Coulomb interactions

A different perspective for nonphotochemical quenching in plant antenna complexes

Light-harvesting complexes of plants exert a dual function of light-harvesting (LH) and photoprotection through processes collectively called nonphotochemical quenching (NPQ). While LH processes are relatively well characterized, those involved in NPQ are less understood. Here, we characterize the quenching mechanisms of CP29, a minor LHC of plants, through the integration of two complementary enhanced-sampling techniques, dimensionality reduction schemes, electronic calculations and the analysis of cryo-EM data in the light of the predicted conformational ensemble. Our study reveals that the switch between LH and quenching state is more complex than previously thought. Several conformations of the lumenal side of the protein occur and differently affect the pigments’ relative geometries and interactions. Moreover, we show that a quenching mechanism localized on a single chlorophyll-carotenoid pair is not sufficient but many chlorophylls are simultaneously involved. In such a diffuse mechanism, short-range interactions between each carotenoid and different chlorophylls combined with a protein-mediated tuning of the carotenoid excitation energies have to be considered in addition to the commonly suggested Coulomb interactions

First-of-its-kind STARD 3 Inhibitor: In Silico Identification and Biological Evaluation as Anticancer Agent

11noSTARD3 is a cellular protein that represents an attractive target for cancer therapy, being overexpressed in breast cancer and implied in the development of colorectal, gastric, and prostate cancers. Unfortunately, no STARD3 inhibitor has been identified yet. In this work, an in silico strategy was applied to predict a reliable binding mode of cholesterol into STARD3 and to develop a pharmacophore-based virtual screening protocol that allowed the identification of the first STARD3 inhibitor ever reported. The identified compound VS1 binds STARD3 with micromolar affinity (IC 50 = 35 μM) and shows antiproliferative activity in breast (MCF7 and MDA- MB-231) and colon (HCT-116) cancer cell lines in the same concentration range (IC 50 = 49.7-105.5 μM). Although VS1 has a moderate potency, we demonstrated that it specifically targets STARD3 in the cells and induces its degradation. Overall, the results confirm the reliability of the computational strategies herein applied and the identification of the first hit compound for the development of novel potent STARD3 inhibitors. © 2019 American Chemical Society.reservedmixedLapillo, Margherita; Salis, Barbara; Palazzolo, Stefano; Poli, Giulio; Granchi, Carlotta; Minutolo, Filippo; Rotondo, Rossella; Caligiuri, Isabella; Canzonieri, Vincenzo; Tuccinardi, Tiziano*; Rizzolio, FlavioLapillo, Margherita; Salis, Barbara; Palazzolo, Stefano; Poli, Giulio; Granchi, Carlotta; Minutolo, Filippo; Rotondo, Rossella; Caligiuri, Isabella; Canzonieri, Vincenzo; Tuccinardi, Tiziano; Rizzolio, Flavi

Antibacterial and Hypoglycemic Diterpenoids from Salvia chamaedryoides

A surface extract of the aerial parts of Salvia chamaedryoides afforded 13 diterpenes (1 1213), with seven compounds (1, 3, 4, 7 129, 12) described for the first time. The structures of the new compounds were established using 1D and 2D NMR spectroscopic methods, HRESIMS, and ECD data. The potential hypoglycemic effects of the crude extract, fractions, and pure compounds from S. chamaedryoides were investigated by inhibition of \u3b1-glucosidase and \u3b1-amylase enzymes. The extract and its fractions showed a moderate dose-dependent inhibition; the pure compounds exhibited differential inhibitory activity against these two enzymes. Molecular modeling studies were also performed to suggest the interaction mode of compound 3 in the \u3b1-glucosidase enzyme active site. The antimicrobial activity of the purified compounds was investigated against 26 clinical pathogens. No activity was detected for the Gram-negative species tested nor on Candida albicans and C. glabrata, while variable susceptibilities were observed using Gram-positive staphylococcal and enterococcal species

Antibacterial and Hypoglycemic Diterpenoids from <i>Salvia chamaedryoides</i>

A surface extract of the aerial parts of <i>Salvia chamaedryoides</i> afforded 13 diterpenes (<b>1</b>–<b>13</b>), with seven compounds (<b>1</b>, <b>3</b>, <b>4</b>, <b>7</b>–<b>9</b>, <b>12</b>) described for the first time. The structures of the new compounds were established using 1D and 2D NMR spectroscopic methods, HRESIMS, and ECD data. The potential hypoglycemic effects of the crude extract, fractions, and pure compounds from <i>S. chamaedryoides</i> were investigated by inhibition of α-glucosidase and α-amylase enzymes. The extract and its fractions showed a moderate dose-dependent inhibition; the pure compounds exhibited differential inhibitory activity against these two enzymes. Molecular modeling studies were also performed to suggest the interaction mode of compound <b>3</b> in the α-glucosidase enzyme active site. The antimicrobial activity of the purified compounds was investigated against 26 clinical pathogens. No activity was detected for the Gram-negative species tested nor on <i>Candida albicans</i> and <i>C. glabrata</i>, while variable susceptibilities were observed using Gram-positive staphylococcal and enterococcal species