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Living organisms are constructed from proteins that assemble into biomolecular complexes, each with a unique shape and function. Our knowledge about the structure–activity relationship of these complexes is still limited, mainly because of their small size, complex structure, fast processes, and changing environment. Furthermore, the constraints of current microscopic tools and the difficulty in applying molecular dynamic simulations to capture the dynamic response of biomolecular complexes and long-term phenomena call for new supplementary tools and approaches that can help bridge this gap. In this paper, we present an approach to comparing biomolecular and origami hierarchical structures and apply it to comparing bacterial microcompartments (BMCs) with spiral-based origami models. Our first analysis compares proteins that assemble the BMC with an origami model called "flasher", which is the unit cell of an assembled origami model. Then, the BMC structure is compared with the assembled origami model and based on the similarity, a physical scaled-up origami model, which is analogous to the BMC, is constructed. The origami model is translated into a computer-aided design model and manufactured via 3D-printing technology. Finite element analysis and physical experiments of the origami model and 3D-printed parts reveal trends in the mechanical response of the icosahedron, which is constructed from tiled-chiral elements. The chiral elements rotate as the icosahedron expands and we deduce that it allows the BMC to open gates for transmembrane passage of materials. [ABSTRACT FROM AUTHOR]

Protein kinases are one of the most significant drug targets in the human proteome, historically harnessed for the treatment of cancer, cardiovascular disease, and a growing number of other conditions, including autoimmune and inflammatory processes. Since the approval of the first kinase inhibitors in the late 1990s and early 2000s, the field has grown exponentially, comprising 98 approved therapeutics to date, 37 of which were approved between 2016 and 2021. While many of these small-molecule protein kinase inhibitors that interact orthosterically with the protein kinase ATP binding pocket have been massively successful for oncological indications, their poor selectively for protein kinase isozymes have limited them due to toxicities in their application to other disease spaces. Thus, recent attention has turned to the use of alternative allosteric binding mechanisms and improved drug platforms such as modified peptides to design protein kinase modulators with enhanced selectivity and other pharmacological properties. Herein we review the role of different protein kinase C (PKC) isoforms in cancer and cardiovascular disease, with particular attention to PKC-family inhibitors. We discuss translational examples and carefully consider the advantages and limitations of each compound (Part I). We also discuss the recent advances in the field of protein kinase modulators, leverage molecular docking to model inhibitor–kinase interactions, and propose mechanisms of action that will aid in the design of next-generation protein kinase modulators (Part II). [ABSTRACT FROM AUTHOR]

Human protein kinases are highly-sought-after drug targets, historically harnessed for treating cancer, cardiovascular disease, and an increasing number of autoimmune and inflammatory conditions. Most current treatments involve small molecule protein kinase inhibitors that interact orthosterically with the protein kinase ATP-binding pocket. As a result, these compounds are often poorly selective and highly toxic. Part I of this series reviews the role of PKC isoforms in various human diseases, featuring cancer and cardiovascular disease, as well as translational examples of PKC modulation applied to human health and disease. In the present Part II, we discuss alternative allosteric binding mechanisms for targeting PKC, as well as novel drug platforms, such as modified peptides. A major goal is to design protein kinase modulators with enhanced selectivity and improved pharmacological properties. To this end, we use molecular docking analysis to predict the mechanisms of action for inhibitor–kinase interactions that can facilitate the development of next-generation PKC modulators. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular diseases are the main cause of mortality in the world. Their most common expression is ischemic heart disease (IHD) such as myocardial infarction (MI). Physical rehabilitation is a common practice for IHD patients. Yet, there is no definition of when is the most effective time to start physical rehabilitation. However, it is recommended to start it as soon as possible. There is a growing interest in understanding the relationship between IHD and cardiomyocytes mitochondrial dynamics processes. Mitochondrial imbalance after MI accelerates cardiac damage. Peptide-based drugs are an effective and safe treatment option., Aims: To examine rehabilitation and peptide intervention post-MI to assess optimal time to start a physical activity and mitochondrial function post-MI., Background: Early training as well as peptide treatment will protect the cardiac muscle post-MI from accelerated damage., Methods: Sixty rats will be divided into 6 groups: Six groups will undergo ischemia-reperfusion (I/R) surgery, by a 30 minute occlusion of their left anterior descending artery (LAD) followed by reperfusion. Three groups will start moderate-intensity exercise training for 8 weeks at different time-points post-MI (3, 7, or 21 days). Another group will be injected with synthetic peptide 5' pre-reperfusion. A sedentary group and a sham group will be used as controls. Results will be assessed by a mitochondrial function test, echocardiography, blood inflammatory and biochemical markers, pressure/volume loops, an exercise test and histology., Results: Improvement of cardiac physiology following exercise training, and mitochondrial treatment will shed light on the preferred timing of cardiac rehabilitation and the mitochondrial damage post-MI.