Journal of proteins and proteomics最新文献

Chondroitin sulfate proteoglycans (CSPGs) are extracellular matrix components composed of linear glycosaminoglycan (GAG) side chains attached to a core protein. CSPGs play a vital role in neurodevelopment, signal transduction, cellular proliferation and differentiation and tumor metastasis through interaction with growth factors and signaling proteins. These pleiotropic functions of proteoglycans are regulated spatiotemporally by the GAG chains attached to the core protein. There are over 70 chondroitin sulfate-linked proteoglycans reported in cells, cerebrospinal fluid and urine. A core glycan linker of 3-6 monosaccharides attached to specific serine residues can be extended by 20-200 disaccharide repeating units making intact CSPGs very large and impractical to analyze. The current paradigm of CSPG analysis involves digesting the GAG chains by chondroitinase enzymes and analyzing either the protein part, the disaccharide repeats, or both by mass spectrometry. This method, however, provides no information about the site of attachment or the composition of linker oligosaccharides and the degree of sulfation and/or phosphorylation. Further, the analysis by mass spectrometry and subsequent identification of novel CSPGs is hampered by technical challenges in their isolation, less optimal ionization and data analysis. Unknown identity of the linker oligosaccharide also makes it more difficult to identify the glycan composition using database searching approaches. Following chondroitinase digestion of long GAG chains linked to tryptic peptides, we identified intact GAG-linked peptides in clinically relevant samples including plasma, urine and dermal fibroblasts. These intact glycopeptides including their core linker glycans were identified by mass spectrometry using optimized stepped higher energy collision dissociation and electron-transfer/higher energy collision dissociation combined with hybrid database search/de novo glycan composition search. We identified 25 CSPGs including three novel CSPGs that have not been described earlier. Our findings demonstrate the utility of combining enrichment strategies and optimized high-resolution mass spectrometry analysis including alternative fragmentation methods for the characterization of CSPGs.

Supplementary information: The online version contains supplementary material available at 10.1007/s42485-022-00092-3.

Metal pollution of water and soil ecosystems has been linked to stress and/or toxicity in plants, thus affecting the quality and productivity of food crops. This condition has further aggravated the essential food demand caused by the increase in the human population. Reports from previous studies have shown that correcting the noxiousness due to metal stress tolerance, requires several modes of action in the systemic, tissue, cellular, physiological, biochemical, and molecular levels in food crops which might be apparent in terms of enhanced productivity. The possible targets of the toxicity impact of metals in food crops are the MG (methylglyoxal) and ROS (reactive oxygen species) which could result in damage to the DNA structure, enzymes inactivation, protein oxidation, and lipids' peroxidation. This current review evaluates insights into proteomics and metabolomics of metal chelation in food crops with special effects on the toxicity, tolerance, and partitioning of metals towards better health. Detailed information on the biochemical and physiological mechanisms of plant stress from metal induction and tolerance was highlighted. The specific information of various tolerance strategies of food crops under trace element toxicity, the function of metabolites, proteins, and food crop hormones in stress tolerance to heavy presences of metal contents in plants is discussed. Information on the partitioning of trace elements in food crops was enlisted. The health benefits and possible risks from the consumption of trace metals in food crops were evaluated followed by recommending the future research directions.

Cytochrome P450 46A1 (CYP46A1) is a crucial enzyme in brain that converts cholesterol to 24 (S) hydroxy cholesterol thereby increasing its polarity to facilitate removal of excess cholesterol from the CNS. The inhibition of CYP46A1 with several synthetic molecules has been investigated extensively for treatment of Alzheimer's disease, Huntington's disease, glaucoma, and in hippocampal neurons from aged mice. However, phytochemicals have received far little attention in studies involving development of potential CYP46A1 inhibitors. Thus, in the present study phytoconstituents from Indian traditional medicinal plants; Bacopa monnieri, Piper longum, and Withania somnifera, were virtually screened for interaction with CYP46A1 using computational tools. Out of three plants, six molecules from P. longum and three molecules from W. somnifera were shortlisted to study interactions with CYP46A1 based on the physio-chemical parameters. Fargesin, piperolactam A and coumaperine from P. longum showed the higher binding affinity and the values were - 10.3, - 9.5, - 9.0 kcal/moles respectively, whereas, withaferin A from W. somnifera had a binding affinity of - 12.9 kcal/mol. These were selected as potential modulators as they exhibited suitable interactions with active site residues; Tyr109, Leu112, Trp368, Gly369, and Ala474. The selected molecules were further subjected to molecular dynamics simulation. Further, the pharmacological properties of molecules were also predicted using ADMET calculator and the data revealed that all the selected compounds had good absorption as well as solubility characteristics. In addition, sesamin, fargesin, piperolactam A, and coumaperine had minimal or no toxic effects. Thus, the study successfully identified compounds from Indian medicinal plants that may serve as potential inhibitors of CYP46A1 or base structures to design novel CYP46A1 inhibitors, which may be effective in treating neurological conditions involving perturbed cholesterol homeostasis.

Supplementary information: The online version contains supplementary material available at 10.1007/s42485-022-00098-x.