Analysis of the Snake Venom Peptidome.

Snake venom peptidomes are known to be a large source of molecules with different pharmacological properties. The complexity and variability of snake venoms, the presence of proteinases, and the lack of complete species-specific genome sequences make snake venom peptidome profiling a challenging task that requires especial technical strategies for sample processing and mass spectrometric analysis. Here, we describe a method for assessing the content of snake venom peptides and highlight the importance of sampling procedures, as they substantially influence the peptidomic complexity of snake venoms.

FDA recommended potent drugs against COVID-19: Insight through molecular docking.

Human Coronavirus (COVID-19) is a worldwide pandemic of 2019-20 that was emerged in China in December 2019. More than 37,000deaths with7, 84, 440confirmed cases has been reported from around 200 different countries has been reported till now and the number is increasing every second. The spread is said to be through human to human transmission via close contact or respiratory droplets produced when people cough or sneeze. No treatment for the illness has been approved yet. The urgent need is to find solution to this growing problem that has affected the whole mankind. World Health Organisation (WHO) as well as US Food and Drug Administration (FDA) are continuously working to find the solution. In the same line they have proposed many potent drugs that may have efficiency against the newly emerged viral infection. To support the efforts the present study is designed to carry out the in silico analysis viz. Docking studies of around 16drugs recently recommended by US FDA by observing the interaction of test molecules with SARS proteinase.

Analysis of the Snake Venom Peptidome.

Snake venom peptidomes are known to be a large source of molecules with different pharmacological properties. The complexity and variability of snake venoms, the presence of proteinases, and the lack of complete species-specific genome sequences make snake venom peptidome profiling a challenging task that requires especial technical strategies for sample processing and mass spectrometric analysis. Here we describe a method for assessing the content of snake venom peptides and highlight the importance of sampling procedures, as they substantially influence the peptidomic complexity of snake venoms.

Analysis of the snake venom peptidome

Snake venom peptidomes are known to be a large source of molecules with different pharmacological properties. The complexity and variability of snake venoms, the presence of proteinases, and the lack of complete species-specific genome sequences make snake venom peptidome profiling a challenging task that requires especial technical strategies for sample processing and mass spectrometric analysis. Here we describe a method for assessing the content of snake venom peptides and highlight the importance of sampling procedures, as they substantially influence the peptidomic complexity of snake venoms.

Inhibitory serpins. New insights into their folding, polymerization, regulation and clearance.

Serpins are a widely distributed family of high molecular mass protein proteinase inhibitors that can inhibit both serine and cysteine proteinases by a remarkable mechanism-based kinetic trapping of an acyl or thioacyl enzyme intermediate that involves massive conformational transformation. The trapping is based on distortion of the proteinase in the complex, with energy derived from the unique metastability of the active serpin. Serpins are the favoured inhibitors for regulation of proteinases in complex proteolytic cascades, such as are involved in blood coagulation, fibrinolysis and complement activation, by virtue of the ability to modulate their specificity and reactivity. Given their prominence as inhibitors, much work has been carried out to understand not only the mechanism of inhibition, but how it is fine-tuned, both spatially and temporally. The metastability of the active state raises the question of how serpins fold, whereas the misfolding of some serpin variants that leads to polymerization and pathologies of liver disease, emphysema and dementia makes it clinically important to understand how such polymerization might occur. Finally, since binding of serpins and their proteinase complexes, particularly plasminogen activator inhibitor-1 (PAI-1), to the clearance and signalling receptor LRP1 (low density lipoprotein receptor-related protein 1), may affect pathways linked to cell migration, angiogenesis, and tumour progression, it is important to understand the nature and specificity of binding. The current state of understanding of these areas is addressed here.

The influence of the amyloid ß-protein and its precursor in modulating cerebral hemostasis.

Ischemic and hemorrhagic strokes are a significant cause of brain injury leading to vascular cognitive impairment and dementia (VCID). These deleterious events largely result from disruption of cerebral hemostasis, a well-controlled and delicate balance between thrombotic and fibrinolytic pathways in cerebral blood vessels and surrounding brain tissue. Ischemia and hemorrhage are both commonly associated with cerebrovascular deposition of amyloid ß-protein (Aß). In this regard, Aß directly and indirectly modulates cerebral thrombosis and fibrinolysis. Further, major isoforms of the Aß precursor protein (AßPP) function as a potent inhibitor of pro-thrombotic proteinases. The purpose of this review article is to summarize recent research on how cerebral vascular Aß and AßPP influence cerebral hemostasis. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

Functional role of transient conformations: Rediscovering "chronosteric effects" thirty years later.

Proteins are dynamic entities that exert, in some cases, their functions via complex pathways, involving active transient species. This phenomenon was highlighted for the first time in 1983 by Antonini et al. (J. Biol. Chem. 258, 4676-4678), who demonstrated that at least one intermediate occurring in the formation of the bovine ß-trypsin-Kunitz inhibitor complex displayed catalytic properties different from those of the active enzyme and of the inactive enzyme-inhibitor adduct. Since it was impossible to explain this phenomenon in terms of static three-dimensional structures, the term "chronosteric effects" was coined to capture the observation that transient species are relevant to protein function(s). Here, some recent results on the folding and function of proteins are reported on the light of chronosteric effects.