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1.
J Mol Recognit ; 35(10): e2979, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35642097

RESUMEN

Infections caused by the bacteria Enterococcus faecalis (also known as E. faecalis) are common in hospitals. This bacterium is resistant to a wide range of medicines and causes a variety of nosocomial infections. An increase in the number of infections caused by multidrug-resistant (MDR) bacteria is causing substantial economic and health issues around the world. Consequently, new therapeutic techniques to tackle the growing threat of E. faecalis infections must be developed as soon as possible. In this regard, we have targeted a protein that is regarded to be critical for the survival of bacteria in this experiment. Homoserine kinase (HSK) is a threonine metabolism enzyme that belongs to the GHMP kinase superfamily. It is a crucial enzyme in threonine metabolism. This enzyme is responsible for a critical step in the threonine biosynthesis pathway. Given the important function that E. faecalis Homoserine Kinase (ESK) plays in bacterial metabolism, we report here cloning, expression, purification and structural studies of E. faecalis HSK using homology modelling. In addition, we have reported on the model's molecular docking and Molecular Dynamic Stimulation (MD Stimulation) investigations to validate the results of the docking experiments. The results were promising. In silico investigations came up with the conclusion: pheniramine has good binding affinity for the E. faecalis HSK.


Asunto(s)
Enterococcus faecalis , Feniramina , Antibacterianos , Enterococcus faecalis/genética , Simulación del Acoplamiento Molecular , Feniramina/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol) , Treonina/metabolismo
2.
J Appl Microbiol ; 133(2): 287-310, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35396804

RESUMEN

There is an intricate network of relations between endophytic fungi and their hosts that affects the production of various bioactive compounds. Plant-associated endophytic fungi contain industrially important enzymes and have the potential to fulfil their rapid demand in the international market to boost business in technology. Being safe and metabolically active, they have replaced the usage of toxic and harmful chemicals and hold a credible application in biotransformation, bioremediation and industrial processes. Despite these, there are limited reports on fungal endophytes that can directly cater to the demand and supply of industrially stable enzymes. The underlying reasons include low endogenous production and secretion of enzymes from fungal endophytes which have raised concern for widely accepted applications. Hence, it is imperative to augment the biosynthetic and secretory potential of fungal endophytes. Modern state-of-the-art biotechnological technologies aiming at strain improvement using cell factory engineering as well as precise gene editing like Clustered Regularly Interspaced Palindromic Repeats (CRISPR) and its Associated proteins (Cas) systems which can provide a boost in fungal endophyte enzyme production. Additionally, it is vital to characterize optimum conditions to grow one strain with multiple enzymes (OSME). The present review encompasses various plants-derived endophytic fungal enzymes and their applications in various sectors. Furthermore, we postulate the feasibility of new precision approaches with an aim for strain improvement and enhanced enzyme production.


Asunto(s)
Endófitos , Hongos , Biotecnología , Endófitos/genética , Endófitos/metabolismo , Hongos/genética , Hongos/metabolismo
3.
Semin Cell Dev Biol ; 96: 77-90, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-30951893

RESUMEN

Phosphorus (P), an essential macronutrient, is pivotal for growth and development of plants. Availability of phosphate (Pi), the only assimilable P, is often suboptimal in rhizospheres. Pi deficiency triggers an array of spatiotemporal adaptive responses including the differential regulation of several transcription factors (TFs). Studies on MYB TF PHR1 in Arabidopsis thaliana (Arabidopsis) and its orthologs OsPHRs in Oryza sativa (rice) have provided empirical evidence of their significant roles in the maintenance of Pi homeostasis. Since the functional characterization of PHR1 in 2001, several other TFs have now been identified in these model plants. This raised a pertinent question whether there are any likely interactions across these TFs. Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system has provided an attractive paradigm for editing genome in plants. Here, we review the applications and challenges of this technique for genome editing of the TFs for deciphering the function and plausible interactions across them. This technology could thus provide a much-needed fillip towards engineering TFs for generating Pi use efficient plants for sustainable agriculture. Furthermore, we contemplate whether this technology could be a viable alternative to the controversial genetically modified (GM) rice or it may also eventually embroil into a limbo.


Asunto(s)
Sistemas CRISPR-Cas/genética , Edición Génica , Homeostasis/genética , Modelos Biológicos , Fosfatos/metabolismo , Plantas/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Variación Genética/genética , Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo
4.
J Mol Recognit ; 34(6): e2886, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33393093

RESUMEN

Entamoeba histolytica (Eh), a parasitic protozoan and the causative agent of invasive Amoebiasis, invade the host tissue through an effective secretory pathway. There are several lines of evidence suggesting that amoebic trophozoite pore-forming complex amoebapore and a large class of proteases enzymes including rhomboid proteases, cysteine proteases, and metalloproteases are implicated in host tissue invasion. For successful delivery of these molecules/cargos, trophozoites heavily rely on sorting machinery from the endoplasmic reticulum, Golgi to plasma membrane. Although, sole secretion machinery in E. histolytica is not characterized yet. Therefore, here our aim is to understand the properties of key molecules N-ethylmaleimide-sensitive fusion protein attached to protein receptors (SNAREs) in E. histolytica. SNAREs proteins are an important component of the membrane-trafficking machinery and have been associated in a range of processes including vesicle tethering, fusion as well as specificity of vesicular transport in all eukaryotic cells. SNARE proteins are architecturally simple, categorized by the presence of one copy of a homologous coiled-coil forming motif. However, the structural information and protein-protein interaction study of Eh-associated syntaxin proteins are still not known. Here, we characterize the syntaxin 1 like molecule and VAMP from Eh through physiochemical profiling, modeling, atomistic simulation, protein-protein interaction, and docking approaches on the proteins containing SNARE and synaptobrevin domain. The modeled structures and the critical residues recognized through protein interaction and docking study may provide better structural and functional insights into these proteins and may aid in the development of newer diagnostic assays.


Asunto(s)
Entamoeba histolytica/metabolismo , Mapas de Interacción de Proteínas/fisiología , Proteínas Qa-SNARE/metabolismo , Secuencia de Aminoácidos , Membrana Celular/metabolismo , Membrana Celular/parasitología , Células Eucariotas/metabolismo , Células Eucariotas/parasitología , Canales Iónicos/metabolismo , Simulación del Acoplamiento Molecular , Estudios Prospectivos , Proteínas Protozoarias/metabolismo , Proteínas R-SNARE/metabolismo , Proteínas SNARE/metabolismo
5.
J Mol Recognit ; 34(9): e2894, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33719110

RESUMEN

Enterococcus faecalis (E. faecalis) is a Gram-positive coccoid, non-sporulating, facultative anaerobic, multidrug resistance bacterium responsible for almost 65% to 80% of all enterococcal nosocomial infections. It usually causes infective endocarditis, urinary tract and surgical wound infections. The increase in E. faecalis resistance to conventionally available antibiotic has rekindled intense interest in developing useful antibacterial drugs. In E. faecalis, diaminopimelate epimerase (DapF) is involved in the lysine biosynthetic pathway. The product of this pathway is precursors of peptidoglycan synthesis, which is a component of bacterial cell wall. Also, because mammals lack this enzyme, consequently E. faecalis diaminopimelate epimerase (EfDapF) represents a potential target for developing novel class of antibiotics. In this regard, we have successfully cloned, overexpressed the gene encoding DapF in BL-21(DE3) and purified with Ni-NTA Agarose resin. In addition to this, binding studies were performed using fluorescence spectroscopy in order to confirm the bindings of the identified lead compounds (acetaminophen and dexamethasone) with EfDapF. Docking studies revealed that acetaminophen found to make hydrogen bonds with Asn72 and Asn13 while dexamethasone interacted by forming hydrogen bonds with Asn205 and Glu223. Thus, biochemical studies indicated acetaminophen and dexamethasone, as potential inhibitors of EfDapF and eventually can reduce the catalytic activity of EfDapF.


Asunto(s)
Acetaminofén/farmacología , Isomerasas de Aminoácido/antagonistas & inhibidores , Dexametasona/farmacología , Enterococcus faecalis/enzimología , Simulación del Acoplamiento Molecular , Isomerasas de Aminoácido/química , Isomerasas de Aminoácido/metabolismo , Proteínas Bacterianas/antagonistas & inhibidores , Sitios de Unión , Reposicionamiento de Medicamentos , Enterococcus faecalis/efectos de los fármacos , Conformación Proteica
6.
Semin Cell Dev Biol ; 74: 123-132, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28903074

RESUMEN

Availability of phosphate (Pi) is often limited in rhizospheres in different agroclimatic zones and adversely affects growth and development of plants. To circumvent this impasse, there is an urgent need and global consensus to develop Pi use efficient crops. To achieve this goal, it is essential to identify the molecular entities that exert regulatory influences on the sensing and signaling cascade governing Pi homeostasis. SIZ1 encodes a small ubiquitin-like modifier (SUMO E3) ligase, and plays a pivotal role in the post-translational SUMOylation of proteins. In this review, we discuss the reverse genetics approach conventionally used for providing circumstantial evidence towards the regulatory influences of SIZ1 on several morphophysiological and molecular traits that govern Pi homeostasis in taxonomically diverse Arabidopsis thaliana (Arabidopsis) and Oryza sativa (rice) model species. However, the efforts have been rather modest in identifying SUMO protein targets that play key roles in the maintenance of Pi homeostasis in these model plants contrary to the plethora of them now known in lower organisms and animals. Therefore, to predict the SIZ1-mediated SUMOylome involved in Pi homeostasis, the state-of-the-art high-throughput technologies often used for animals thus provide an attractive paradigm towards achieving the long-term goal of developing Pi use efficient crops.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Homeostasis , Ligasas/metabolismo , Oryza/metabolismo , Fosfatos/metabolismo , Sumoilación , Arabidopsis/química , Oryza/química
7.
J Mol Recognit ; 32(12): e2808, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31432591

RESUMEN

The enteric protozoan parasite, Entamoeba histolytica (Eh), is the causative agent of amoebic dysentery and liver abscess in humans. It infects around 50 million people worldwide, which is a third general cause of death from parasitic diseases after malaria and schistosomiasis. The other prevalent form of the disease is Visceral leishmaniasis caused by Leishmania donovani which is a human blood parasite. On the other hand, the Toxoplasma gondii is an obligate intracellular protozoan parasite; it causes serious opportunistic infections in HIV-positive persons. The biological processes in all living organisms are mostly mediated by the proteins, and recognizing new target proteins and finding their function in pathogenesis will help in choosing better diagnostic markers. In eukaryotes, Rab protein plays a major role in pathogenesis. Rabs represent the largest branch in the Ras superfamily of GTPases. Among them, the Rab5 is important in the endocytosis and thus involved in pathogenesis. In this paper, we discussed the physiochemical profiling, modelling, and docking of the Rab5 protein from pathogenic species that is Entamoeba histolytica, Leishmania donovani, and Toxoplasma gondii. The modeled structures from this study and the key residues identified would give a better understanding of the three-dimensional structure and functional insights into these proteins and help in developing new drug targets.


Asunto(s)
Simulación por Computador , Entamoeba histolytica/metabolismo , Leishmania donovani/metabolismo , Toxoplasma/metabolismo , Proteínas de Unión al GTP rab5/química , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Enlace de Hidrógeno , Ligandos , Simulación del Acoplamiento Molecular , Homología Estructural de Proteína , Proteínas de Unión al GTP rab5/genética
8.
J Mol Recognit ; 32(11): e2802, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31353747

RESUMEN

Enterococcus faecalis is a gram-positive, rod-shape bacteria responsible for around 65% to 80% of all enterococcal nosocomial infections. It is multidrug resistant (MDR) bacterium resistant to most of the first-line antibiotics. Due to the emergence of MDR strains, there is an urgent need to find novel targets to develop new antibacterial drugs against E. faecalis. In this regard, we have identified naphthoate synthase (1,4-dihydroxy-2-naphthoyl-CoA synthase, EC: 4.1.3.36; DHNS) as an anti-E. faecalis target, as it is an essential enzyme for menaquinone (vitamin K2 ) synthetic pathway in the bacterium. Thus, inhibiting naphtholate synthase may consequently inhibit the bacteria's growth. In this regard, we report here cloning, expression, purification, and preliminary structural studies of naphthoate synthase along with in silico modeling, molecular dynamic simulation of the model and docking studies of naphthoate synthase with quercetin, a plant alkaloid. Biochemical studies have indicated quercetin, a plant flavonoid as the potential lead compound to inhibit catalytic activity of EfDHNS. Quercetin binding has also been validated by spectrofluorimetric studies in order to confirm the bindings of the ligand compound with EfDHNS at ultralow concentrations. Reported studies may provide a base for structure-based drug development of antimicrobial compounds against E. faecalis.


Asunto(s)
Enterococcus faecalis/enzimología , Inhibidores Enzimáticos/farmacología , Hidroliasas/antagonistas & inhibidores , Quercetina/farmacología , Clonación Molecular , Simulación por Computador , Cristalización , Enterococcus faecalis/efectos de los fármacos , Hidroliasas/química , Hidroliasas/metabolismo , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Quercetina/química
9.
Curr Pharm Des ; 30(3): 161-168, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38243948

RESUMEN

Sepsis is a complex clinical condition and a leading cause of death worldwide. During Sepsis, there is a derailment in the host response to infection, which can progress to severe sepsis and multiple organ dysfunction or failure, which leads to death. Free radicals, including reactive oxygen species (ROS) generated predominantly in mitochondria, are one of the key players in impairing normal organ function in sepsis. ROS contributing to oxidative stress has been reported to be the main culprit in the injury of the lung, heart, liver, kidney, gastrointestinal, and other organs. Here in the present review, we describe the generation, and essential properties of various types of ROS, their effect on macromolecules, and their role in mitochondrial dysfunction. Furthermore, the mechanism involved in the ROS-mediated pathogenesis of sepsis-induced organ dysfunction has also been discussed.


Asunto(s)
Enfermedades Mitocondriales , Sepsis , Humanos , Especies Reactivas de Oxígeno , Insuficiencia Multiorgánica , Radicales Libres , Sepsis/patología , Estrés Oxidativo
10.
Brain Sci ; 14(6)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38928554

RESUMEN

Protein kinase C (PKC) is a diverse enzyme family crucial for cell signalling in various organs. Its dysregulation is linked to numerous diseases, including cancer, cardiovascular disorders, and neurological problems. In the brain, PKC plays pivotal roles in synaptic plasticity, learning, memory, and neuronal survival. Specifically, PKC's involvement in Alzheimer's Disease (AD) pathogenesis is of significant interest. The dysregulation of PKC signalling has been linked to neurological disorders, including AD. This review elucidates PKC's pivotal role in neurological health, particularly its implications in AD pathogenesis and chronic alcohol addiction. AD, characterised by neurodegeneration, implicates PKC dysregulation in synaptic dysfunction and cognitive decline. Conversely, chronic alcohol consumption elicits neural adaptations intertwined with PKC signalling, exacerbating addictive behaviours. By unravelling PKC's involvement in these afflictions, potential therapeutic avenues emerge, offering promise for ameliorating their debilitating effects. This review navigates the complex interplay between PKC, AD pathology, and alcohol addiction, illuminating pathways for future neurotherapeutic interventions.

11.
Artículo en Inglés | MEDLINE | ID: mdl-38291210

RESUMEN

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) is a desirable gene modification tool covering a wide area in various sectors of medicine, agriculture, and microbial biotechnology. The role of this incredible genetic engineering technology has been extensively investigated; however, it remains formidable with cargo choices, nonspecific delivery, and insertional mutagenesis. Various nanomaterials including lipid, polymeric, and inorganic are being used to deliver the CRISPR-Cas system. Progress in nanomaterials could potentially address these challenges by accelerating precision targeting, cost-effectiveness, and one-step delivery. In this review, we highlighted the advances in nanotechnology and nanomaterials as smart delivery systems for CRISPR-Cas so as to ameliorate applications for environmental remediation including biomedical research and healthcare, strategies for mitigating antimicrobial resistance, and to be used as nanofertilizers for enhancing crop growth, and reducing the environmental impact of traditional fertilizers. The timely co-evolution of nanotechnology and CRISPR technologies has contributed to smart novel nanostructure hybrids for improving the onerous tasks of environmental remediation and biological sustainability.

12.
Int Immunopharmacol ; 118: 110100, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37011501

RESUMEN

Entamoeba histolytica (Eh), a microaerophilic parasite, causes deadly enteric infections that result in Amoebiasis. Every year, the count of invasive infections reaches 50 million approximately and 40,000 to 1,00,000 deaths occurring due to amoebiasis are reported globally. Profound inflammation is the hallmark of severe amoebiasis which is facilitated by immune first defenders, neutrophils. Due to size incompatibility, neutrophils are unable to phagocytose Eh and thus, came up with the miraculous antiparasitic mechanism of neutrophil extracellular traps (NETs). This review provides an in-depth analysis of NETosis induced by Eh including the antigens involved in the recognition of Eh and the biochemistry of NET formation. Additionally, it underscores its novelty by describing the dual role of NETs in amoebiasis where it acts as a double-edged sword in terms of both clearing and exacerbating amoebiasis. It also provides a comprehensive account of the virulence factors discovered to date that are implicated directly and indirectly in the pathophysiology of Eh infections through the lens of NETs and can be interesting drug targets.


Asunto(s)
Entamoeba histolytica , Entamebiasis , Trampas Extracelulares , Entamebiasis/tratamiento farmacológico , Entamebiasis/epidemiología , Entamebiasis/fisiopatología , Neutrófilos , Sistemas de Liberación de Medicamentos , Humanos , Antígenos Nucleares
13.
Diagnostics (Basel) ; 13(2)2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36673087

RESUMEN

Sepsis is one of the deadliest disorders in the new century due to specific limitations in early and differential diagnosis. Moreover, antimicrobial resistance (AMR) is becoming the dominant threat to human health globally. The only way to encounter the spread and emergence of AMR is through the active detection and identification of the pathogen along with the quantification of resistance. For better management of such disease, there is an essential requirement to approach many suitable diagnostic techniques for the proper administration of antibiotics and elimination of these infectious diseases. The current method employed for the diagnosis of sepsis relies on the conventional culture of blood suspected infection. However, this method is more time consuming and generates results that are false negative in the case of antibiotic pretreated samples as well as slow-growing microbes. In comparison to the conventional method, modern methods are capable of analyzing blood samples, obtaining accurate results from the suspicious patient of sepsis, and giving all the necessary information to identify the pathogens as well as AMR in a short period. The present review is intended to highlight the culture shift from conventional to modern and advanced technologies including their limitations for the proper and prompt diagnosing of bloodstream infections and AMR detection.

14.
Biochim Biophys Acta ; 1813(10): 1700-7, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21722677

RESUMEN

Nitric oxide synthase (NOS) expression and catalytic status in human peripheral blood mononuclear cells (PBMCs) is debatable, while its sub-cellular distribution remains unascertained. The present study characterizes NOS transcripts by real time PCR, NOS protein by immunoprecipitation (IP)/Western blot (WB), nitric oxide (NO) generation by DAF-2DA and NOS sub-cellular distribution by immunogold electron microscopy in resting PBMCs, monocytes and lymphocytes obtained from healthy donors. We observed constitutive expression of full length NOS isoforms (nNOS, iNOS and eNOS) in PBMCs: with the highest expression of iNOS in comparison to nNOS and eNOS. Isolated monocytes expressed more eNOS transcript and protein as compared to nNOS and iNOS. Lymphocytes however had more iNOS transcripts and protein than nNOS and eNOS. NOS was catalytically active in PBMCs, monocytes as well as in lymphocytes as evident by NO generation in the presence of substrate and cofactors, which was significantly reduced in the presence of NOS inhibitor. Immunogold electron microscopy and morphometric analysis revealed the distinct pattern of NOS distribution in monocytes and lymphocytes and also exhibited differences in the nuclear-cytoplasmic ratio. nNOS localization was much more in the cytosol than in the nucleus among both monocytes and lymphocytes. Interestingly, iNOS distribution was comparable in both cytosol and nucleus among monocytes, but in lymphocytes iNOS was predominantly localized to the cytosol. The present study exhibits constitutive presence of all the NOS isoforms in PBMCs and reports the distinct pattern of NOS distribution among monocytes and lymphocytes.


Asunto(s)
Leucocitos Mononucleares/metabolismo , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa/metabolismo , Células Cultivadas , Clonación Molecular , Humanos , Espacio Intracelular/metabolismo , Isoenzimas/química , Isoenzimas/genética , Isoenzimas/metabolismo , Leucocitos Mononucleares/ultraestructura , Linfocitos/metabolismo , Linfocitos/ultraestructura , Microscopía Electrónica , Monocitos/metabolismo , Monocitos/ultraestructura , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/química , Distribución Tisular
15.
Cytometry A ; 81(3): 238-47, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22170804

RESUMEN

Neutrophils expel extracellular traps (NETs) to entrap and exterminate the invaded micro-organisms. Acute/chronic inflammatory disorders are often observed with aberrantly enhanced NETs formation and high nitric oxide (NO) availability. Recent study from this laboratory demonstrated release of NETs from human neutrophils following treatment with SNP or SNAP. This study is an extension of our previous finding to explore the extracellular bacterial killing, source of DNA in the expelled NETs, their ability to induce proinflammatory cytokines release from platelets/THP-1 cells, and assessment of NO-mediated free radical formation by using a consistent NO donor, DETA-NONOate. NO-mediated NETs exhibited extracellular bacterial killing as determined by colony forming units. NO-mediated NETs formation was due to the activation of NADPH oxidase and myeloperoxidase. NO- or PMA-mediated NETs were positive for both nuclear and mitochondrial DNA as well as proteolytic enzymes. Incubation of NETs with human platelets enhanced the release of IL-1ß and IL-8, while with THP-1 cells, release of IL-1ß, IL-8, and TNFα was observed. This study demonstrates that NO by augmenting enzymatic free radical generation release NETs to promote extracellular bacterial killing. These NETs were made up of mitochondrial and nuclear DNA and potentiated release of proinflammatory cytokines.


Asunto(s)
ADN Mitocondrial/metabolismo , ADN/metabolismo , Inflamación/inmunología , Activación Neutrófila , Neutrófilos/citología , Neutrófilos/metabolismo , Adulto , Plaquetas/metabolismo , Radicales Libres , Humanos , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Mitocondrias/genética , NADPH Oxidasas/metabolismo , Óxido Nítrico/biosíntesis , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Peroxidasa/metabolismo , Factor de Necrosis Tumoral alfa
16.
Microbiol Res ; 261: 127061, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35605309

RESUMEN

The regulation of the activity of proteases by endogenous inhibitors is a common trend in almost all forms of life. Here, we review the endogenous inhibitors of cysteine proteases of three major pathogenic parasitic protozoa. The review focuses on members of the genus Plasmodium, Entamoeba, and Leishmania. Research in this domain has revealed the presence of only chagasin-like inhibitors of cysteine proteases that house a ß-barrel immunoglobulin-fold and inhibit the target proteases using a 3-loop inhibitory mechanism in these pathogens. Inhibitors of cysteine proteases are highly evolvable enzymes that target a broad spectrum of pathogenic cysteine proteases with a proclivity for those involved in host-parasite interactions. A common trend reflects a limited sequence homology between cysteine proteases and their inhibitors. The inhibitors are also known to participate in other housekeeping functions of the parasites. Generalizations about their roles are thus best avoided. In this review, the reader will find comprehensive information on the cellular localization of inhibitors of cysteine proteases, their structure, function, and the associated mechanisms of action. The reader will also find a thorough analysis of the role of these inhibitors in parasite pathology and the common trends interlinking them with parasite biology and evolution.


Asunto(s)
Proteasas de Cisteína , Parásitos , Secuencia de Aminoácidos , Animales , Inhibidores de Cisteína Proteinasa/farmacología , Proteínas Protozoarias
17.
Curr Protein Pept Sci ; 23(4): 248-263, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35619261

RESUMEN

Enterococcus faecalis (E. faecalis) is an opportunistic multidrug-resistant (MDR) pathogen found in the guts of humans and farmed animals. Due to the occurrence of (MDR) strain there is an urgent need to look for an alternative treatment approach. E. faecalis is a Gram-positive bacterium, which is among the most prevalent multidrug resistant hospital pathogens. Its ability to develop quorum sensing (QS) mediated biofilm formation further exacerbates the pathogenicity and triggers lifethreatening infections. Therefore, developing a suitable remedy for curing E. faecalis mediated enterococcal infections is an arduous task. Several putative virulence factors and proteins are involved in the development of biofilms in E. faecalis. Such proteins often play important roles in virulence, disease, and colonization by pathogens. The elucidation of the structure-function relationship of such protein drug targets and the interacting compounds could provide an attractive paradigm towards developing structure-based drugs against E. faecalis. This review provides a comprehensive overview of the current status, enigmas that warrant further studies, and the prospects toward alleviating the antibiotic resistance in E. faecalis. Specifically, the role of biofilm and quorum sensing (QS) in the emergence of MDR strains had been elaborated along with the importance of the protein drug targets involved in both the processes.


Asunto(s)
Biopelículas , Farmacorresistencia Bacteriana Múltiple , Enterococcus faecalis , Percepción de Quorum , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas/metabolismo , Enterococcus faecalis/efectos de los fármacos , Virulencia , Factores de Virulencia/genética
18.
Curr Protein Pept Sci ; 23(4): 211-225, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35598240

RESUMEN

S-adenosylhomocysteine nucleosidase (MTAN) is a protein that plays a crucial role in several pathways of bacteria that are essential for its survival and pathogenesis. In addition to the role of MTAN in methyl-transfer reactions, methionine biosynthesis, and polyamine synthesis, MTAN is also involved in bacterial quorum sensing (QS). In QS, chemical signaling autoinducer (AI) secreted by bacteria assists cell to cell communication and is regulated in a cell density-dependent manner. They play a significant role in the formation of bacterial biofilm. MTAN plays a major role in the synthesis of these autoinducers. Signaling molecules secreted by bacteria, i.e., AI-1 are recognized as acylated homoserine lactones (AHL) that function as signaling molecules within bacteria. QS enables bacteria to establish physical interactions leading to biofilm formation. The formation of biofilm is a primary reason for the development of multidrug-resistant properties in pathogenic bacteria like Enterococcus faecalis (E. faecalis). In this regard, inhibition of E. faecalis MTAN (EfMTAN) will block the QS and alter the bacterial biofilm formation. In addition to this, it will also block methionine biosynthesis and many other critical metabolic processes. It should also be noted that inhibition of EfMTAN will not have any effect on human beings as this enzyme is not present in humans. This review provides a comprehensive overview of the structural-functional relationship of MTAN. We have also highlighted the current status, enigmas that warrant further studies, and the prospects for identifying potential inhibitors of EfMTAN for the treatment of E. faecalis infections. In addition to this, we have also reported structural studies of EfMTAN using homology modeling and highlighted the putative binding sites of the protein.


Asunto(s)
N-Glicosil Hidrolasas , Percepción de Quorum , Bacterias/metabolismo , Biopelículas , Homocisteína , Humanos , Metionina , N-Glicosil Hidrolasas/química , N-Glicosil Hidrolasas/metabolismo
19.
Biomed Res Int ; 2022: 5058121, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35309178

RESUMEN

Chronic obstructive pulmonary disease (COPD) is pulmonary emphysema characterized by blockage in the airflow resulting in the long-term breathing problem, hence a major cause of mortality worldwide. Excessive generation of free radicals and the development of chronic inflammation are the major two episodes underlying the pathogenesis of COPD. Currently used drugs targeting these episodes including anti-inflammatory, antioxidants, and corticosteroids are unsafe, require high doses, and pose serious side effects. Nanomaterial-conjugated drugs have shown promising therapeutic potential against different respiratory diseases as they are required in small quantities which lower overall treatment costs and can be effectively targeted to diseased tissue microenvironment hence having minimal side effects. Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) are safe as their breakdown products are easily metabolized in the body. Drugs loaded on the PLGA NPs have been shown to be promising agents as anticancer, antimicrobial, antioxidants, and anti-inflammatory. Surface modification of PLGA NPs can further improve their mechanical properties, drug loading potential, and pharmacological activities. In the present review, we have presented a brief insight into the pathophysiological mechanism underlying COPD and highlighted the role, potential, and current status of PLGA NPs loaded with drugs in the therapy of COPD.


Asunto(s)
Nanopartículas , Enfermedad Pulmonar Obstructiva Crónica , Antioxidantes/uso terapéutico , Portadores de Fármacos , Glicoles , Humanos , Ácido Láctico , Nanopartículas/uso terapéutico , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico
20.
Plants (Basel) ; 11(22)2022 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-36432862

RESUMEN

Moringa oleifera Lam. (MO) is a fast-growing drought-resistant tree belonging to the family Moringaceae and native to the Indian subcontinent and cultivated and/or naturalized worldwide with a semi-arid climate. MO is also popularly known as a miracle tree for its repertoire of nutraceutical, pharmacological, and phytochemical properties. The MO germplasm is collected, conserved, and maintained by various institutions across the globe. Various morphological, biochemical, and molecular markers are used for determining the genetic diversity in MO accessions. A higher yield of leaves and pods is often desirable for making various products with commercial viability and amenable for trade in the international market. Therefore, breeding elite varieties adapted to local agroclimatic conditions and in vitro propagation are viable and sustainable approaches. Here, we provide a comprehensive overview of MO germplasm conservation and various markers that are employed for assessing the genetic diversity among them. Further, breeding and in vitro propagation of MO for various desirable agronomic traits are discussed. Finally, trade and commerce of various functional and biofortified foods and non-food products are enumerated albeit with a need for a rigorous and stringent toxicity evaluation.

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