Structural characterization and in-silico analysis of Momordica charantia 7S globulin for stability and ACE inhibition

Abstract

Momordica charantia (Mc) seeds are widely used edible crop with high nutritional quality. The food and pharmaceutical industries use it as a natural anti-oxygenic agent. Herein, a ~52 kDa protein, which is a major part of seed proteome has been purified, biochemically characterized and structure has been determined. MALDI-ESI-MS identified peptide fragments and contig-deduced sequence suggested the protein to be homologous to 7S globulins. The crystal structure shows that protein has a bicupin fold similar to 7S globulins and the electron density for a copper and acetate ligand were observed in the C-terminal barrel domain. In silico study reveals that a tripeptide (VFK) from Mc7S possess a higher binding affinity for angiotensin converting enzyme (ACE) than already reported drug Lisinopril (LPR). The protein is a glycoprotein and highly stable under varying thermal and pH conditions due to its secondary structures. The DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay showed the protein to have an anti-oxygenic nature and can aid in scavenging free radical from sample. The protein can assist to enhance the nutritional and functional value of food by acting as a food antioxidant. Further, characterization of Mc7S required which might add in importance of Mc7S as antioxidant, anti-diabetic and anti-hypertensive. Momordica charantia (Mc) commonly known as bitter melon or bitter gourd is a member of Cucurbitaceae family, which grows in tropical and subtropical areas. The plant is known for centuries in Ayurveda for its anti-bacterial, anti-fungal, anti-viral, anti-parasitic, hypoglycemic, anti-fertility, anti-tumorous, and anti-carcinogenic properties 1-5. It is preferred as a medication for a broad range of health applications, including the treatment of dysmenorrhea, eczema, emmenagogue, galactagogue, gout, jaundice, kidney (stone), leprosy, leucorrhea, piles, pneumonia, psoriasis, rheumatism, scabies, T2DM (type 2 diabetes mellitus), obesity, hypertension, bacterial and viral infections, cancer, and even AIDS 1-5. It contains biologically active molecules including proteins, triterpenes, saponins, steroids, flavonoids, alkaloids, and acids 6. Each part of plant i.e. seeds, roots, leaves and especially unripe fruits has its pharmacological properties 4. The juice is used to cure a large number of conditions such as for articular pain relief and chronic fever in jaundice, liver disease, and digestive system diseases because of laxative, diuretic, and anti-helminthic effects. In the case of chronic skin diseases, it is applied locally to treat boils, burns, and rash. Moreover, components of Mc plant i.e. unripe fruit, seeds and aerial parts are largely known for its anti-diabetic properties due to the presence of insulin-mimetic in the seeds 7,8. The aqueous seed extract of Mc also scavenges the free radicals for protection against lipid peroxidation thereby reducing the risk of diabetic complications 9. The strong anti-oxygenic activity may be due to the presence of phenolic compounds and saponins 10. The globula...

Computational guided identification of novel potent inhibitors of N-terminal domain of nucleocapsid protein of severe acute respiratory syndrome coronavirus 2

“…Molecular dynamics simulation of NTD with GMP, ZINC000257324845, ZINC000005169973 and ZINC000009913056 were performed to assess the structural and dynamics variation at an atomistic level. Protein topologies and coordinates files were generated using GROMACS 2019.2 along with GROMOS96 43a1 force field, as done by Kesari et al (2020), Singh et al (2018), van Gunsteren et al (1996), van der Spoel et al (2005. Total four systems (NTD-GMP, NTD-ZINC000257324845, NTD-ZINC000005169973 and NTD-ZINC000009913056) were generated and kept for molecular simulation of 100 ns.…”

“…Three chlorides (Cl -) ions were added using genion tool to neutralize the system. The final production run was done for 100 ns, and coordinates were updated every 10 ps, as done by Kesari et al (2020). The trajectories were analyzed by visual molecular dynamics (VMD) and XMGRACE (Humphrey et al, 1996).…”

Compounds of plants with activity against SARS-CoV-2 targets

“…In addition, lunasin was an effective adjuvant for immunization with OVA, which together improved animal survival against lethal challenge with influenza virus expressing the major histocompatibility complex (MHC) class I OVA peptide SIINFEKL (PR8-OTI) Preclinical in vivo [ 62 ] Equol 20 mg/kg for 3 days by gavage ( G. max ) In BALB/c mice treated with equol showed a significantly higher level of OVA-specific IgE. IL-13 (produced mainly by CD4⁺ T cells) production level was significantly higher than that control Preclinical in vivo [ 29 ] 7S globulin ( Momordica charantia L. – Cucurbitaceae) Study revealed that a tripeptide (VFK) from 7S globulin possess a higher binding affinity for ACE than reported drug Lisinopril (LPR) Not mentioned [ 42 ] Lectin 100 µg/ml ( M. charantia ) Lectin is a T cell-independent B cell activator and a polyclonal immunoglobulin (Ig) inducer in BALB/c mice. Additionally, lectin was shown to upregulate the cell activation marker CD86, in a B cell subpopulation Preclinical in vivo [ 63 ] MAP30 (anti-HIV protein) 1 µM ( M. charantia ) MAP30 was capable of inhibiting infection of HIV type 1 (HIV-1) in T lymphocytes and monocytes as well as replication of the virus in already-infected cells.…”

Three Selected Edible Crops of the Genus Momordica as Potential Sources of Phytochemicals: Biochemical, Nutritional, and Medicinal Values

“…Generally, extracts from Momordica spp. are useful for the treatment of various diseases and many other ailments due to the several biological activities exerted such as anti-diabetic Tan et al (2008) , Madala et al (2014) , Jia et al (2017) , Islam and Jalaluddin (2019) , Perera et al (2021) , Venugopal and Dhanasekaran (2021) , anti-oxidant Acquaviva et al (2013) , Ozusaglam and Karakoca (2013) , Huang et al (2020) , Perumal et al (2021) , anti-microbial ( Kumar et al (2009) , Patel et al (2010) , Gupta et al (2011) , anti-bacterial ( Koneri et al (2006) , Orhan et al (2010) , Leelaprakash et al (2011) , Puškárová et al (2017) , Chen et al (2019) , Islam and Jalaluddin (2019) , Khadijeh et al (2019) , anti-viral Orhan et al (2010) , Santhosh Kumar et al (2020) , anti-fungal Santos et al (2012) , anthelmintic Beloin et al (2005) , Jia et al (2017) , insecticidal Pari et al (2020) , antiglycation Chen et al (2011) , anti-inflammatory Chen et al (2019) , Khadijeh et al (2019) , Perera et al (2021) , Venugopal and Dhanasekaran (2021) , anti-thrombotic Patil and Rathod (2020) , anti-allergic Asna et al (2020) , hepatoprotective Ramalhete et al (2011) , estrogenic Badhwar et al (2020) , hypolipidemic effect Aeri and Raj (2020) , anti-carcinogenic Kesari et al (2020) , anti-proliferative Yue et al (2020) , anti-mutagenic Rolnik and Olas (2020) , and chemo-preventive activities ( Gupta, 2020 ).…”