The transimination reaction involves conversion of an internal aldimine involving pyridoxal 5′-phosphate (PLP) and an enzyme to an external aldimine involving PLP and a substrate amino acid and it constitutes an essential step in many biological processes catalyzed by PLP-dependent enzymes. We have investigated the free energy landscape and mechanistic pathways of the transimination process at the active site of aspartate aminotransferase by means of hybrid quantum–classical molecular dynamics simulations combined with various enhanced sampling techniques. It is found that, after a geminal diamine is formed in the first step of the process, the reaction proceeds through a path where a proton from the amine nitrogen of the substrate amino acid is transferred first to the phenolic oxygen of the PLP ring, and from there, it is transferred to the imine nitrogen of the active site lysine in the next step of the reaction. Both of these proton transfer events are found to be assisted by relative rotation of the PLP ring which brings the phenolic oxygen of PLP closer to the amine and imine nitrogens of the substrate and lysine, respectively. The transfer of the proton from the phenolic oxygen of PLP to the active site lysine residue is found to be the rate-determining step with an effective barrier of only 4 kcal/mol. Neither any direct proton transfer from lysine to the substrate nor any indirect proton transfer involving any active site residue or water is found.

We have performed hybrid quantum-classical metadynamics simulations and quantum chemical calculations to investigate the free energy landscapes of intramolecular proton transfer and associated tautomeric equilibrium in pyridoxal 5 '-phosphate (PLP) Schiff Bases, namely the internal and external aldimines, at the active site of serine hydroxymethyltransferase (SHMT) enzyme in aqueous medium. It is important to determine the relative stability of the two tautomers (ketoenamine and enolimine) of the PLP aldimines to study the catalytic activity of the concerned enzyme. Both the internal PLP aldimine (PLP-LYS) and the external PLP aldimine (PLP-SER) of SHMT are found to have a higher stability for the ketoenamine tautomer over the enolimine form. The higher stability of the ketoenamine tautomer can be attributed to the more number of favorable interactions of the ketoenamine form with its surroundings at the active site of the enzyme. The ketoenamine is found to be stabilized by about 2.5 kcal/mol in the PLP-LYS internal aldimine, while this stabilization is about 6.7 kcal/mol for the PLP-SER external aldimine at the active site of the enzyme compared to the corresponding enolimine forms. The interactions faced by the PLP aldimines at the active site pocket determine the relative dominance of the tautomers and could possibly alter the tautomeric shift in different PLP dependent enzymes. © 2018 Wiley Periodicals, Inc.

The newly emerging and re-emerging of viral contagion in the present scenario are of more extensive health concern. After a long calm of many years, an unexpected eruption of the Cat Que Virus in China is a source of our concern. Cat Que Virus is an Arbovirus and belongs to the Simbu serogroup of the Orthobunyavirus genus of the Bunyaviridae family. The Simbu serogroup is an extremely diverse group of Arbovirus. The arboviruses are causing the infection in multiple hosts including humans and various livestock. They can cause mild to lifethreatening infections. Arboviruses expand their spectrum and are more observable in recent times. Human actions have the most significant geophysical impact on the environment. Changes in rainfall patterns, floods, and the risk of extreme weather events are all consequences of climate change. These events may be connected to the extension of permissive vectors, geographic ranges, and therefore provide more chance of growth and spread of potential vector. Arboviruses are responsible for the health hazard to millions of people globally. It is critical to concentrate research and surveillance on these emerging and reemerging viruses, particularly arthropod-borne viral infections. The appropriate research and surveillance on them will help us for the development of effective control and treatment strategies and also reduce health problems. The present review summarizes the current broad outline of discovery, evolution and dispersal of this unknown virus.

Serine hydroxymethyltransferase (SHMT) is a ubiquitous enzyme belonging to the fold type I or aspartate aminotransferase (AspAT) family of the pyridoxal 5′-phosphate (PLP)dependent enzymes. Like other PLP-dependent enzymes, SHMT also undergoes the so-called transimination reaction before exhibiting its enzymatic activity. The transimination process constitutes an important pre-step for all PLP-dependent enzymes, where an internal aldimine of the PLP−enzyme complex gets converted to an external aldimine of the substrate−PLP complex at the active site of the enzyme. In case of the transimination reaction involving SHMT, the PLP molecule bound to the active site lysine residue of SHMT (internal aldimine) gets detached from the enzyme by a serine substrate to produce an external aldimine complex, where the PLP is now bound to the serine substrate. In the current study, the free energy surfaces and reaction pathways of different steps of the transimination reaction at the active site of SHMT are investigated by employing hybrid quantum mechanical/molecular mechanical (QM/MM) simulations combined with metadynamics methods of rare event sampling. It is found that the process of transimination involving serine and PLP at the active site of the SHMT enzyme takes place through different elementary steps such as the formation of the first geminal diamine intermediate (GDI1), transfer of a proton from the substrate serine to the phenolic oxygen of PLP, followed by another proton transfer from PLP to the amine nitrogen of lysine with the formation of the second geminal diamine intermediate (GDI2), and finally, detachment of the active site lysine residue from PLP to produce the external aldimine.

Several infections have emerged in humans, domestic animals, wildlife, and plant populations, causing a severe problem for humanity. Since the discovery of the Monkeypox virus (Mpox) in 1958 in Copenhagen, Denmark, it has resurfaced several times, producing severe infections in humans and resulting in a significant fatality rate. Mpox is an Orthopoxvirus of the Poxviridae family. This family contains various medically important viruses. The natural reservoir of Mpox is unknown yet. Mpox might be carried by African rodents and nonhuman primates (such as monkeys). The role of monkeys has been confirmed by its various outbreaks. The infection may be transferred from unidentified wild animals to monkeys, who can then spread it to humans by crossing species barriers. In close contact, human-to-human transmission is also possible. Mpox outbreaks have been documented regularly in Central and Western Africa, but recently in 2022, it has spread to over one hundred-six countries. There is no specific treatment for it, although the smallpox vaccine, antivirals, and vaccinia immune globulin help in the effective management of Mpox. In conclusion: Monkeypox poses a severe threat to public health due to the lack of specific vaccinations and effective antivirals. Surveillance studies in affected regions can assist in the early diagnosis of disease and help to control significant outbreaks. The present review provides information on epidemiology, clinical symptoms, risk factors, diagnosis, and preventive measures of Mpox.