Verma S

References (13)

Title : Recent advances and structure-activity relationship studies of DPP-4 inhibitors as anti-diabetic agents - Singhal_2024_Bioorg.Chem_146_107277
Author(s) : Singhal S , Manikrao Patil V , Verma S , Masand N
Ref : Bioorg Chem , 146 :107277 , 2024
Abstract : Diabetes mellitus (DM) is one of the largest public health problems worldwide and in the last decades various therapeutic targets have been investigated. For the treatment of type-2 DM (T2DM), dipeptidyl peptidase-4 (DPP-4) is one of the well reported target and has established safety in terms of cardiovascular complexicity. Preclinical and clinical studies using DPP-4 inhibitors have demonstrated its safety and effectiveness and have lesser risk of associated hypoglycaemic effect making it suitable for elderly patients. FDA has approved a number of structurally diverse DPP-4 inhibitors for clinical use. The present manuscript aims to focus on the well reported hybrid and non-hybrid analogues and their structural activity relationship (SAR) studies. It aims to provide structural insights for this class of compounds pertaining to favourable applicability of selective DPP-4 inhibitors in the treatment of T2DM.
ESTHER : Singhal_2024_Bioorg.Chem_146_107277
PubMedSearch : Singhal_2024_Bioorg.Chem_146_107277
PubMedID: 38493634

Title : Archaeal lipolytic enzymes: Current developments and further prospects - Meghwanshi_2022_Biotechnol.Adv__108054
Author(s) : Meghwanshi GK , Verma S , Srivastava V , Kumar R
Ref : Biotechnol Adv , :108054 , 2022
Abstract : Lipolytic enzymes include triacylglycerol lipases (EC and esterases (EC that catalyze the cleavage and formation of ester bonds. They are potential industrial biocatalysts because of their broad range of activities on natural and synthetic substrates, high stability in organic solvents, thermal stability, stability in highly acidic and alkaline pH conditions and enantio-, regio- and chemo-selectivity. They also have varied applications in different sectors, among which industrial biotechnology, the production of cleaning agents, and pharmaceuticals are the most important ones. Identifying extremophilic lipolytic enzymes is of paramount interest and is a growing field in academic and industrial research. This review is focused on the current knowledge and future avenues of investigation on lipolytic enzymes sourced from the underexploited archaeal domain. Archaea is a potential source for novel extremophilic enzymes, which have high demand in the industries. The archaeal lipases and esterases are clustered into different families based on their similarity/dissimilarity at the genetic level and protein structures. The updated information on characterized and putative lipase sequences has also been presented in this paper. Common structural scaffolds of archaeal lipases have been deduced and discussed in this review. However, huge diversity at the level of their genetic sequences has yet to be correlated with the structure-function relationship. Based on their biochemical properties, possible applications and future prospective of archaeal lipolytic enzymes have also been proposed.
ESTHER : Meghwanshi_2022_Biotechnol.Adv__108054
PubMedSearch : Meghwanshi_2022_Biotechnol.Adv__108054
PubMedID: 36307049

Title : Current perspectives for microbial lipases from extremophiles and metagenomics - Verma_2021_Biochimie__
Author(s) : Verma S , Meghwanshi GK , Kumar R
Ref : Biochimie , : , 2021
Abstract : Microbial lipases are most broadly used biocatalysts for environmental and industrial applications. Lipases catalyze the hydrolysis and synthesis of long acyl chain esters and have a characteristic folding pattern of alpha/beta hydrolase with highly conserved catalytic triad (Serine, Aspartic/Glutamic acid and Histidine). Mesophilic lipases (optimal activity in neutral pH range, mesophilic temperature range, atmospheric pressure, normal salinity, non-radio-resistant, and instability in organic solvents) have been in use for many industrial biotransformation reactions. However, lipases from extremophiles can be used to design biotransformation reactions with higher yields, less byproducts or useful side products and have been predicted to catalyze those reactions also, which otherwise are not possible with the mesophilic lipases. The extremophile lipase perform activity at extremes of temperature, pH, salinity, and pressure which can be screened from metagenome and de novo lipase design using computational approaches. Despite structural similarity, they exhibit great diversity at the sequence level. This diversity is broader when lipases from the bacterial, archaeal, plant, and animal domains/kingdoms are compared. Furthermore, a great diversity of novel lipases exists and can be discovered from the analysis of the dark matter - the unexplored nucleotide/metagenomic databases. This review is an update on extremophilic microbial lipases, their diversity, structure, and classification. An overview on novel lipases which have been detected through analysis of the genomic dark matter (metagenome) has also been presented.
ESTHER : Verma_2021_Biochimie__
PubMedSearch : Verma_2021_Biochimie__
PubMedID: 33421499

Title : Diversifying Arena of Drug Synthesis: In the Realm of Lipase Mediated Waves of Biocatalysis - Verma_2021_Catalysts_11_1328
Author(s) : Verma S , Choudhary RN , Kanadje AP , Banerjee UC
Ref : Catalysts , 11 :1328 , 2021
Abstract : Hydrolases, being most prominent enzymes used in industrial processes have left no stone unturned in fascinating the pharmaceutical industry. Lipases, being a part of acyl hydrolases are the ones that function similarly to esterases (except an interfacial action) wherein they generally catalyze the hydrolysis of ester bonds. Be it in terms of stereoselectivity or regioselectivity, lipases have manifested their promiscuous proficiency in rendering biocatalytic drug synthesis and intermediates thereof. Industrial utilization of lipases is prevalent since decades ago, but their distinctive catalytic competencies have rendered them suitable for maneuverability in various tides of biocatalytic industrial process development. Numbers of exquisite catalysts have been fabricated out of lipases using nanobiotechnology whereby enzyme reusability and robustness have been conferred to many of the organic synthesis procedures. This marks a considerable achievement of lipases in the second wave of biocatalysis. Furthermore, in the third wave an advent of genetic engineering has fostered an era of customized lipases for suitable needs. Be it stability or an enhanced efficacy, genetic engineering techniques have ushered an avenue for biocatalytic development of drugs and drug intermediates through greener processes using lipases. Even in the forthcoming concept of co-modular catalytic systems, lipases may be the frontiers because of their astonishing capability to act along with other enzymes. The concept may render feasibility in the development of cascade reactions in organic synthesis. An upcoming wave demands fulfilling the vision of tailored lipase whilst a far-flung exploration needs to be unveiled for various research impediments in rendering lipase as a custom fit biocatalyst in pharmaceutical industry.
ESTHER : Verma_2021_Catalysts_11_1328
PubMedSearch : Verma_2021_Catalysts_11_1328

Title : Structural and functional insights about unique extremophilic bacterial lipolytic enzyme from metagenome source - Kaur_2020_Int.J.Biol.Macromol__
Author(s) : Kaur R , Kumar R , Verma S , Kumar A , Rajesh C , Sharma PK
Ref : Int J Biol Macromol , : , 2020
Abstract : In the present investigation, a lipid hydrolyzing gene RPK01was cloned from metagenome source of hot spring. Expression and purification of recombinant protein revealed a protein band of ~24 KDa on 12% SDS-PAGE and is well corroborated with the deduced molecular weight calculated from its amino acid sequence. The purified protein displayed high activity towards short chain fatty acids and was found to be completely stable at 30 degrees C till 3h, and retained ~40% activity at 50 degrees C and 60 degrees C temperature till 3h. Additionally, the pH stability assay showed its functionality in broad range pH, with maximum stability observed at pH2.0, it decreases from pH4.0 to pH12.0 and has retained ~ 40% activity in these pHs. Both circular dichroism and intrinsic Trp fluorescence studies revealed conformational stability of protein structure in wide range of temperature and pH. Enzyme activity enhances in presence of non-ionic surfactants like Tween 20 and TritonX-100. Further, inhibitors of the active site residues including PMSF and DEPC alone were unable to inhibit enzyme activity, while cumulative presence of calcium and inhibitors reduces enzyme activity to 90% indicating conformational changes in the protein. Molecular simulation dynamics analysis revealed a calcium binding site near the lid helix (Asn75-Ile80).
ESTHER : Kaur_2020_Int.J.Biol.Macromol__
PubMedSearch : Kaur_2020_Int.J.Biol.Macromol__
PubMedID: 32088224
Gene_locus related to this paper: bacce-BC4862

Title : Cloning, Characterization, and Structural Modeling of an Extremophilic Bacterial Lipase Isolated from Saline Habitats of the Thar Desert - Verma_2020_Appl.Biochem.Biotechnol__
Author(s) : Verma S , Kumar R , Kumar P , Sharma D , Gahlot H , Sharma PK , Meghwanshi GK
Ref : Appl Biochem Biotechnol , : , 2020
Abstract : Lipases have a characteristic folding pattern of alpha/beta-hydrolase with mostly parallel beta-sheets, flanked on both sides by alpha-helixes in the structure. The active site is formed by a catalytic triad (serine, aspartic/glutamic acid, and histidine), which is highly conserved. In this study, we have used an integrated experimental and computational approach to identify the extremophilic microbial lipases from the saline habitats of the Thar Desert of Rajasthan. Lipase-producing bacteria were screened and a few samples showed significant lipase activity in both quantitative and qualitative experiments. 16S rRNA sequence analysis of the isolate F1 showed that its sequence is quite similar to that of Bacillus licheniformis and Bacillus haynesii, indicating that this isolate belongs to a new subspecies of Bacillus. The isolate F7 showed maximum sequence identity with Bacillus tequilensis strain 10b. The isolate F7 sequence analysis provided a clear testimony that it can be a new strain of Bacillus tequilensis. The F7 lipase exhibited optimal activity at 60 degrees C and pH 9. Structural modeling of the F7 lipase revealed that it has a highly conserved alpha/beta hydrolase fold at the sequence and structural level except for the N-terminal region. Interestingly, residue Glu128 was different from the template structure and showed the hydrogen bonding between the side chain of Glu128 and side chains of Asn35 and Gln152 amino acids. Besides, this amino acid also showed salt bridge interaction between Glu128--Lys101. These interactions may be assisting in preserving the stability and activity of lipase at high temperatures and in alkaline pH conditions. The information gathered from this investigation will guide in the rational designing of new more potential extremophilic lipase.
ESTHER : Verma_2020_Appl.Biochem.Biotechnol__
PubMedSearch : Verma_2020_Appl.Biochem.Biotechnol__
PubMedID: 32424739
Gene_locus related to this paper: 9baci-F7lip

Title : Anti-Acetylcholinesterase Activities of Mono-Herbal Extracts and Exhibited Synergistic Effects of the Phytoconstituents: A Biochemical and Computational Study - Balkrishna_2019_Molecules_24_
Author(s) : Balkrishna A , Pokhrel S , Tomer M , Verma S , Kumar A , Nain P , Gupta A , Varshney A
Ref : Molecules , 24 : , 2019
Abstract : Alzheimer's disease (AD), a neurodegenerative disease, is the most common form of dementia. Inhibition of acetylcholinesterase (AChE) is a common strategy for the treatment of AD. In this study, aqueous, hydro-methanolic, and methanolic extracts of five potent herbal extracts were tested for their in vitro anti-AChE activity. Among all, the Tinospora cordifolia (Giloy) methanolic fraction performed better with an IC50 of 202.64 microg/mL. Of the HPLC analyzed components of T. cordifolia (methanolic extract), palmatine and berberine performed better (IC50 0.66 and 0.94 microg/mL, respectively) as compared to gallic acid and the tool compound "galantamine hydrobromide" (IC50 7.89 and 1.45 microg/mL, respectively). Mode of inhibition of palmatine and berberine was non-competitive, while the mode was competitive for the tool compound. Combinations of individual alkaloids palmatine and berberine resulted in a synergistic effect for AChE inhibition. Therefore, the AChE inhibition by the methanolic extract of T. cordifolia was probably due to the synergism of the isoquinoline alkaloids. Upon molecular docking, it was observed that palmatine and berberine preferred the peripheral anionic site (PAS) of AChE, with pi-interactions to PAS residue Trp286, indicating that it may hinder the substrate binding by partially blocking the entrance of the gorge of the active site or the product release.
ESTHER : Balkrishna_2019_Molecules_24_
PubMedSearch : Balkrishna_2019_Molecules_24_
PubMedID: 31752124

Title : Identification of new members of alkaliphilic lipases in archaea and metagenome database using reconstruction of ancestral sequences - Verma_2019_3.Biotech_9_165
Author(s) : Verma S , Kumar R , Meghwanshi GK
Ref : 3 Biotech , 9 :165 , 2019
Abstract : The application of bioinformatics in lipase research has the potential to discover robust members from different genomic/metagenomic databses. In this study, we explored the diversity and distribution of alkaliphilic lipases in archaea domain and metagenome data sets through phylogenetic survey. Reconstructed ancestral sequence of alkaphilic lipase was used to search the homologous alkaliphilic lipases among the archaea and metagenome public databases. Our investigation revealed a total 21 unique sequences of new alkaliphilic lipases in the archaeal and environmental metagenomic protein databases that shared significant sequence similarity to the bacterial alkaliphilic lipases. Most of the identified new members of alkaliphilic lipases belong to class Haloarchaea. The searched list of homologs also comprised of one characterized lipase from alkalohyperthermophilic Archaeoglobus fulgidus. All the newly identified alkaliphilic lipase members showed conserved pentapeptide [X-His-Ser-X-Gly] motif, a key feature of lipase family. Furthermore, detailed analysis of all these new sequences showed homology either with thermostable or alkalophilic lipases. The reconstructed ancestral sequence-based searches increased the sensitivity and efficacies to detect remotely homologous sequences. We hypothesize that this study can enrich our current knowledge on lipases in designing more potential thermo-alkaliphilic lipases for industrial applications.
ESTHER : Verma_2019_3.Biotech_9_165
PubMedSearch : Verma_2019_3.Biotech_9_165
PubMedID: 30997302

Title : Biodegradation of di-n-butyl phthalate by psychrotolerant Sphingobium yanoikuyae strain P4 and protein structural analysis of carboxylesterase involved in the pathway - Mahajan_2019_Int.J.Biol.Macromol_122_806
Author(s) : Mahajan R , Verma S , Kushwaha M , Singh D , Akhter Y , Chatterjee S
Ref : Int J Biol Macromol , 122 :806 , 2019
Abstract : A priority pollutant Phthalate Esters (PAEs) are widely used as plasticizers and are responsible mainly for carcinogenicity and endocrine disruption in human. For the bioremediation of PAEs, a psychrotolerant Sphingobium yanoikuyae strain P4, capable of utilizing many phthalates dimethyl phthalate (DMP), diethyl phthalate (DEP), dinbutyl phthalate (DBP), diisobutyl phthalate (DIBP), butyl benzyl phthalate (BBP), and few Polycyclic Aromatic Hydrocarbons as the sole source of carbon and energy was isolated from Palampur, Kangra, Himachal Pradesh, India. 100% utilization of DBP (1gL(-1)) by the strain was observed within 24h of incubation at 28 degrees C. Interestingly the strain also degraded DBP completely at 20 degrees C and 15 degrees C within 36h and 60h, respectively. Esterase involved in DBP degradation was found to be inducible in nature and intracellular. Comparative sequence analysis of carboxylesterase enzyme sequences revealed conserved motifs: G-X-S-X-G and -HGG- which were the characteristic peptide motifs reported in different esterases. Structural analysis showed that the enzyme belongs to serine hydrolase superfamily, which has an alpha/beta hydrolase fold. Interaction and binding of DBP to a catalytic Ser(184) residue in the esterase enzyme were also analysed. In conclusion, carboxylesterase possess the required active site which may be involved in the catabolism of DBP.
ESTHER : Mahajan_2019_Int.J.Biol.Macromol_122_806
PubMedSearch : Mahajan_2019_Int.J.Biol.Macromol_122_806
PubMedID: 30395899
Gene_locus related to this paper: sphya-k9da91

Title : Profenofos, an Acetylcholinesterase-Inhibiting Organophosphorus Pesticide: A Short Review of Its Usage, Toxicity, and Biodegradation - Kushwaha_2016_J.Environ.Qual_45_1478
Author(s) : Kushwaha M , Verma S , Chatterjee S
Ref : J Environ Qual , 45 :1478 , 2016
Abstract : Pesticides play an important role in the protection of different crops. Among the diverse sets of pesticides used all over the world, the organophosphates are the most widely used group. Profenofos [O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate] is one of the most largely used organophosphate insecticides on field crops, vegetables, and fruit crops. The World Health Organization classifies this compound as moderately hazardous (Toxicity Class II), and its residues have been found in vegetables like okra [ (L.) Moench], gooseberries ( sp.), green chilies [ (L.)], curry leaves [ (L.) Spreng], mint leaves [ (L.)], and coriander leaves [ (L.)]. Dietary intake of profenofos (PFF) is the major exposure pathway for humans. When applied to agricultural fields, PFF residues spread into every part of the environment: ambient air, surface water, and soil. In this review, we discuss the worldwide usage of PFF pesticide, its toxic effects on humans and other living organisms in the environment, and biodegradation of this chemical by various microbial strains. To date, no complete biodegradation pathway has been established for PFF pesticide, calling for a study of this nature.
ESTHER : Kushwaha_2016_J.Environ.Qual_45_1478
PubMedSearch : Kushwaha_2016_J.Environ.Qual_45_1478
PubMedID: 27695768

Title : Alzheimer's disease like pathology induced six weeks after aggregated amyloid-beta injection in rats: increased oxidative stress and impaired long-term memory with anxiety-like behavior - Sharma_2016_Neurol.Res__1
Author(s) : Sharma S , Verma S , Kapoor M , Saini A , Nehru B
Ref : Neurol Res , :1 , 2016
Abstract : OBJECTIVES: Amyloid-beta (Abeta) peptide deposition into insoluble plaques is a pathological hallmark of Alzheimer's disease (AD), but soluble oligomeric Abeta is considered to be more potent and has been hypothesized to directly impair learning and memory. Also, evidences from some clinical studies indicated that Abeta oligomer formation is the major cause for early AD onset. However, the biochemical mechanism involved in the oligomer-induced toxicity is not very well addressed. So, thise present study was undertaken to study the effects of single intracerebroventricular (icv) injection of protofibrillar Abeta 1-42 on the behavioral and biochemical profile in rats.
METHODS: Rats were divided into two groups (n = 8 per group): (1) sham control group and (2) Abeta 1-42 injected group. A single dose of protofibrillar Abeta 1-42 (5 ul) through icv injection was bilaterally administered into the dorsal hippocampus, while sham control animals were administered with 5 microl of vehicle.
RESULTS: The results demonstrated that the protofibrillar Abeta significantly inhibited long-term memory retention and increased anxiety levels as shown by the behavioral studies. The amyloid deposits were present inside the brain even six weeks after injection as confirmed by thioflavin-T staining and the neurodegeneration induced by these deposits was confirmed by Nissl's staining in hippocampal and cortical regions. The amyloid aggregates induced reactive oxygen species (ROS) production, acetylcholinesterase activity, nitrite levels, lipid peroxidation, and inhibited antioxidant enzyme activity in hippocampus, cortex, and striatum regions of rat brain after six weeks. DISCUSSION: The present study indicated that protofibrillar Abeta 1-42 injection altered long term memory, induced anxiety-like behavior and also developed Alzheimer's disease like pathology in rats.
ESTHER : Sharma_2016_Neurol.Res__1
PubMedSearch : Sharma_2016_Neurol.Res__1
PubMedID: 27431920

Title : Draft genome sequencing and secretome analysis of fungal phytopathogen Ascochyta rabiei provides insight into the necrotrophic effector repertoire - Verma_2016_Sci.Rep_6_24638
Author(s) : Verma S , Gazara RK , Nizam S , Parween S , Chattopadhyay D , Verma PK
Ref : Sci Rep , 6 :24638 , 2016
Abstract : Constant evolutionary pressure acting on pathogens refines their molecular strategies to attain successful pathogenesis. Recent studies have shown that pathogenicity mechanisms of necrotrophic fungi are far more intricate than earlier evaluated. However, only a few studies have explored necrotrophic fungal pathogens. Ascochyta rabiei is a necrotrophic fungus that causes devastating blight disease of chickpea (Cicer arietinum). Here, we report a 34.6 megabase draft genome assembly of A. rabiei. The genome assembly covered more than 99% of the gene space and 4,259 simple sequence repeats were identified in the assembly. A total of 10,596 high confidence protein-coding genes were predicted which includes a large and diverse inventory of secretory proteins, transporters and primary and secondary metabolism enzymes reflecting the necrotrophic lifestyle of A. rabiei. A wide range of genes encoding carbohydrate-active enzymes capable for degradation of complex polysaccharides were also identified. Comprehensive analysis predicted a set of 758 secretory proteins including both classical and non-classical secreted proteins. Several of these predicted secretory proteins showed high cysteine content and numerous tandem repeats. Together, our analyses would broadly expand our knowledge and offer insights into the pathogenesis and necrotrophic lifestyle of fungal phytopathogens.
ESTHER : Verma_2016_Sci.Rep_6_24638
PubMedSearch : Verma_2016_Sci.Rep_6_24638
PubMedID: 27091329
Gene_locus related to this paper: didra-a0a162vf33 , didra-a0a162w3h8 , didra-a0a162wlb9 , didra-a0a162wpi1 , didra-a0a162xw12 , didra-a0a162y9j3 , didra-a0a162yh98 , didra-a0a163a9b7 , didra-a0a163akw2 , didra-a0a163ana9 , didra-a0a163b1b6 , didra-a0a163b4m8 , didra-a0a163bnc3 , didra-a0a163cl26 , didra-a0a163cy94 , didra-a0a163d5r6 , didra-a0a163dil1 , didra-a0a163ekx7 , didra-a0a163f365 , didra-a0a163f846 , didra-a0a163fb98 , didra-a0a163fym5 , didra-a0a163g5c5 , didra-a0a163lvf3 , didra-a0a163met1 , didra-a0a163mhi9 , didra-a0a163mjg9 , didra-a0a163mlk1 , didra-a0a162wpr0 , didra-a0a162zv92 , didra-a0a163di22 , didra-a0a163cx35

Title : Drug resistance and neurotransmitter receptors of nematodes: recent studies on the mode of action of levamisole - Martin_2005_Parasitol_131 Suppl_S71
Author(s) : Martin RJ , Verma S , Levandoski M , Clark CL , Qian H , Stewart M , Robertson AP
Ref : Parasitology , 131 Suppl :S71 , 2005
Abstract : Here we review recent studies on the mode of action of the cholinergic anthelmintics (levamisole, pyrantel etc.). We also include material from studies on the free living nematode Caenorhabditis elegans. The initial notion that these drugs act on a single receptor population, while attractive, has proven to be an oversimplification. In both free living and parasitic nematodes there are multiple types of nicotinic acetylcholine receptor (nAChR) on the somatic musculature. Each type has different (sometimes subtly so) pharmacological properties. The implications of these findings are: (1) combinations of anthelmintic that preferentially activate a broad range of nAChR types would be predicted to be more effective; (2) in resistant isolates of parasite where a subtype has been lost, other cholinergic anthelmintics may remain effective. Not only are there multiple types of nAChR, but relatively recent research has shown these receptors can be modulated; it is possible to increase the response of a parasite to a fixed concentration of drug by altering the receptor properties (e.g. phosphorylation state). These findings offer a potential means of increasing efficacy of existing compounds as an alternative to the costly and time consuming development of new anthelmintic agents.
ESTHER : Martin_2005_Parasitol_131 Suppl_S71
PubMedSearch : Martin_2005_Parasitol_131 Suppl_S71
PubMedID: 16569294