Characterization of VldE (Spr1875), a Pneumococcal Two-State l,d-Endopeptidase with a Four-Zinc Cluster in the Active Site.

Remodeling of the pneumococcal cell wall, carried out by peptidoglycan (PG) hydrolases, is imperative for maintaining bacterial cell shape and ensuring survival, particularly during cell division or stress response. The protein Spr1875 plays a role in stress response, both regulated by the VicRK two-component system (analogous to the WalRK TCS found in Firmicutes). Modular Spr1875 presents a putative cell-wall binding module at the N-terminus and a catalytic C-terminal module (Spr1875) connected by a long linker.

Molecular docking aided machine learning for the identification of potential VEGFR inhibitors against renal cell carcinoma.

Renal cell carcinoma is a highly vascular tumor associated with vascular endothelial growth factor (VEGF) expression. The Vascular Endothelial Growth Factor -2 (VEGF-2) and its receptor was identified as a potential anti-cancer target, and it plays a crucial role in physiology as well as pathology. Inhibition of angiogenesis via blocking the signaling pathway is considered an attractive target.

Designing a novel drug-drug conjugate as a prodrug for breast cancer therapy: in silico insights.

Breast cancer (BC) poses a significant global health threat, necessitating innovative therapeutic approaches. The ribosomal s6 kinase 2 (RSK2) has emerged as a promising target due to its roles in cell proliferation and survival. This study proposes a drug-drug conjugate prodrug comprising Methotrexate (hydrophobic) and Capecitabine (hydrophilic) for BC treatment.

Prediction of deleterious non-synonymous SNPs of TMPRSS2 protein combined with Molecular Dynamics Simulations and free energy analysis to identify the potential peptide substrates against SARS-CoV-2.

Globally the SARS-CoV-2 viral infection demands for the new drugs, the TMPRSS2 target plays a vital role in facilitating the virus entry. The aim of the present study is to identify the potential peptide substrate from the Anti-viral database against TMPRSS2 of SARS-CoV-2. The compound screening and variation analysis were performed using molecular docking analysis and online tools such as PROVEAN and SNAP2 server, respectively.

Structural characterization of lytic transglycosylase MltD of Pseudomonas aeruginosa, a target for the natural product bulgecin A.

Natural product bulgecin A potentiates the activity of β-lactam antibiotics by inhibition of three lytic transglycosylases in Pseudomonas aeruginosa, of which MltD is one. MltD exhibits both endolytic and exolytic reactions in the turnover of the cell-wall peptidoglycan and tolerates the presence or absence of stem peptides in its substrates. The present study reveals structural features of the multimodular MltD, presenting a catalytic module and four cell-wall-binding LysM modules that account for these attributes.

In silico approaches for the identification of potential allergens among hypothetical proteins from Alternaria alternata and its functional annotation.

Direct exposure to the fungal species Alternaria alternata is a major risk factor for the development of asthma, allergic rhinitis, and inflammation. As of November 23rd 2020, the NCBI protein database showed 11,227 proteins from A. alternata genome as hypothetical proteins (HPs).

Catalytic process of anhydro-N-acetylmuramic acid kinase from Pseudomonas aeruginosa.

The bacterial cell envelope is the structure with which the bacterium engages with, and is protected from, its environment. Within this envelop is a conserved peptidoglycan polymer which confers shape and strength to the cell envelop. The enzymatic processes that build, remodel, and recycle the chemical components of this cross-linked polymer are preeminent targets of antibiotics and exploratory targets for emerging antibiotic structures.

Combination of bendamustine-azacitidine against Syk target of breast cancer: an study.

Breast cancer (BC) is the most serious and second leading cause of death in women worldwide. When breast cancer is diagnosed and treated early, the chance of long-term survival is up to 90%. On the other hand, 90% of BC patient deaths are due to metastasis and a lack of effective early diagnosis.

Computational exploration of molecular flexibility and interaction of meropenem analogs with the active site of oxacillinase-23 in .

Carbapenem-resistant is an opportunistic pathogen responsible for nosocomial infections and is one of the biggest global threats according to the World Health Organization (WHO), particularly causing substantial morbidity and mortality. This study aimed at using computational approaches to screen meropenem and its analogs against OXA-23-positive analyzing the correlations between kinetic and phenotypic characteristics. A total of 5,450 compounds were screened using virtual screening workflow (HTVS, Glide-SP, and Glide-XP) to identify the best compounds based on their binding energy and interactions against OXA-23 and OXA-27 as they had phenotypic data available.

Molecular dynamics simulation of Toxin-Antitoxin (TA) system in Acinetobacter baumannii to explore the novel mechanism for inhibition of cell wall biosynthesis: Zeta Toxin as an effective therapeutic target.

The majority of bacteria and archaea contains Toxin-Antitoxin system (TA) that codes for the stable Toxin and unstable Antitoxin components forming a complex. The Antitoxin inhibits the catalytic activities of the Toxin. In general, the Antitoxin will be degraded by the proteases leading to the Toxin activation that subsequently targets essential cellular processes, including transcription, translation, replication, cell division, and cell wall biosynthesis.

Screening of Natural Phytocompounds Towards Identification of Potential Lead Compounds to Treat COVID-19.

COVID-19 is one of the members of the coronavirus family that can easily assail humans. As of now, 10 million people are infected and above two million people have died from COVID-19 globally. Over the past year, several researchers have made essential advances in discovering potential drugs.

Atomistic simulation on flavonoids derivatives as potential inhibitors of bacterial gyrase of .

The bacterial DNA gyrase is an attractive target to identify the novel antibacterial agents. The flavonoid derivatives possess various biological activities such as antimicrobial, anti-inflammatory and anticancer activities. The aim of present study is to identify the potential molecule from flavonoid derivatives against using atomistic simulation namely Molecular Docking, Quantum Chemical and Molecular Dynamics.

Exploring the Catalytic Reaction of Cysteine Proteases.

Cysteine proteases play a major role in many life processes and are the target of key drugs. The reaction mechanism of these enzymes is a complex process, which involves several steps that are divided into two main groups: acylation and deacylation. In this work, we studied the energy profile for the acylation and a part of the deacylation reaction of three different enzymes, cruzain, papain, and the Q19A-mutated papain with the benzyloxycarbonyl-phenylalanylarginine-4-methylcoumaryl-7-amide (CBZ-FR-AMC) substrate.

approach of naringin as potent phosphatase and tensin homolog (PTEN) protein agonist against prostate cancer.

Prostate cancer (PC) is one of the major impediments affecting men, which leads approximately 31,620 deaths in both developing and developed countries. Although some chemotherapy drugs have been reported for prostate cancer, they are not effective due to the lack of safety, efficacy and low selectivity. Hence, the novel alternative anticancer agents with remarkable effect are highly appreciable.

Molecular docking, dynamics and free energy analyses of OXA class enzymes with carbapenems investigating their hydrolytic mechanisms.

is a critical priority pathogen listed by the World Health Organization due to increasing levels of resistance to carbapenem classes of antibiotics. It causes wound and other nosocomial infections, which can be life-threatening. Hence, there is an urgent need for the development of new classes of antibiotics.

The prevalence and drug resistance pattern of extended spectrum β-lactamases (ESBLs) producing Enterobacteriaceae in Africa.

Extended spectrum β-lactamases (ESBLs) are a group of enzymes that can hydrolyze a variety of β-lactams including fourth generation cephalosporins and compromise the efficacy of all β-lactams, except cephamycins and carbapenems. In the worldwide, the ESBL group of enzymes are found widely and causes a severe infection on human health which leads to various diseases. This review primarily focusses on analyzing the prevalence and drug resistance patterns in the African continent.

Biomimetic synthesis of silver nanoparticles from and their potential anticancer activity against human breast cancer cells.

Silver nanoparticles (AgNPs) have been undeniable for its antimicrobial activity while its antitumour potential is still limited. Therefore, the present study focused on determining cytotoxic effects of AgNPs on Michigan cancer foundation-7 (MCF-7) breast cancer cells and its corresponding mechanism of cell death. Herein, the authors developed a bio-reduction method for AgNPs synthesis using actinomycetes isolated from marine soil sample.

Exploring the Development of Ground-State Destabilization and Transition-State Stabilization in Two Directed Evolution Paths of Kemp Eliminases.

Computer-aided enzyme design presents a major challenge since in most cases it has not resulted in an impressive catalytic power. The reasons for the problems with computational design include the use of nonquantitative approaches, but they may also reflect other difficulties that are not completely obvious. Thus, it is very useful to try to learn from the trend in directed evolution experiments.