High Molecular Weight Kininogen: A Review of the Structural Literature

Kininogens are multidomain glycoproteins found in the blood of most vertebrates. High molecular weight kininogen demonstrate both carrier and co-factor activity as part of the intrinsic pathway of coagulation, leading to thrombin generation. Kininogens are the source of the vasoactive nonapeptide bradykinin. To date, attempts to crystallize kininogen have failed, and very little is known about the shape of kininogen at an atomic level. New advancements in the field of cryo-electron microscopy (cryoEM) have enabled researchers to crack the structure of proteins that has been refractory to traditional crystallography techniques. High molecular weight kininogen is a good candidate for structural investigation by cryoEM. The goal of this review is to summarize the findings of kininogen structural studies.

Assessment of Globularity of Protein Structures via Minimum Volume Ellipsoids and Voxel-Based Atom Representation

A computer algorithm for assessment of globularity of protein structures is presented. By enclosing the input protein in a minimum volume ellipsoid (MVEE) and calculating a profile measuring how voxelized space within this shape (cubes on a uniform grid) is occupied by atoms, it is possible to estimate how well the molecule resembles a globule. For any protein to satisfy the proposed globularity criterion, its ellipsoid profile (EP) should first confirm that atoms adequately fill the ellipsoid’s center. This property should then propagate towards the surface of the ellipsoid, although with diminishing importance. It is not required to compute the molecular surface. Globular status (full or partial) is assigned to proteins with values of their ellipsoid profiles, called here the ellipsoid indexes (EI), above certain levels. Due to structural outliers which may considerably distort the measurements, a companion method for their detection and reduction of their influence is also introduced. It is based on kernel density estimation and is shown to work well as an optional input preparation step for MVEE. Finally, the complete workflow is applied to over two thousand representatives of SCOP 2.08 domain superfamilies, surveying the landscape of tertiary structure of proteins from the Protein Data Bank.

Coronavirus Diseases (COVID-19): Features, Epidemiology, Mutational variations and Treatments Across India

Coronaviruses are a group of enveloped viruses with a longer, undivided single-stranded RNA genome, which cause diseases in a variety of animals and humans. In addition to infecting other economically important animals (such as pigs or chickens), six coronaviruses are known to infect human hosts, causing respiratory illness. Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are highly pathogenic animal coronaviruses that have produced local, regional, and worldwide outbreaks. It is suspected that the current pandemic, caused by a similar coronavirus (SARS-CoVID-19). A new variant of B.1.617 lineage that causes worry about many countries has been identified first in the UK but it makes the worst scenario in India. This includes mutants with immune prolapse E484K and N501Y mutations. Some new variants recently discovered in India like double & triple mutation due to some specific climatic and environmental conditions. Because it creates a viral exodermis and contacts human cells due to mutations in peplomer proteins. The other type of protein is spike protein, are required to bind to receptors in human cells mutations. It can improve the affinity for human receptors and increase the virus, they can cause immune prolapse and reinfection. Moreover, these viruses are capable of adapting and mutating to the new environment. Our immune system is unable to distinguish them from previous infections due to changes in the structure of proteins. The rapid transmission of the COVID-19 around the world causing a severe mortality rate depends on mutation on their spike protein.

D-Amino Acids and D-Amino Acid-Containing Peptides: Potential Disease Biomarkers and Therapeutic Targets?

In nature, amino acids are found in two forms, L and D enantiomers, except for glycine which does not have a chiral center. The change of one form to the other will lead to a change in the primary structure of proteins and hence may affect the function and biological activity of proteins. Indeed, several D-amino acid-containing peptides (DAACPs) were isolated from patients with cataracts, Alzheimer’s and other diseases. Additionally, significant levels of free D-amino acids were found in several diseases, reflecting the disease conditions. Studying the molecular mechanisms of the DAACPs formation and the alteration in D-amino acids metabolism will certainly assist in understanding these diseases and finding new biomarkers and drug targets. In this review, the presence of DAACPs and free D-amino acids and their links with disease development and progress are summarized. Similarly, we highlight some recent advances in analytical techniques that led to improvement in the discovery and analysis of DAACPs and D-amino acids.

AlphaFold2: A role for disordered protein prediction?

The development of AlphaFold2 was a paradigm-shift in the structural biology community; herein we assess the ability of AlphaFold2 to predict disordered regions against traditional sequence-based disorder predictors. We find that a naive use of Dictionary of Secondary Structure of Proteins (DSSP) to separate ordered from disordered regions leads to a dramatic overestimation in disorder content, and that the Predicted Aligned Error (PAE) provides a much more rigorous metric. In addition, we show that even when used for disorder prediction, conventional predictors can outperform the PAE in disorder identification, and note an interesting relationship between the PAE and secondary structure that may explain our observations and hints at a broader application of the PAE to IDP dynamics.

Graph Coverings for Investigating Non Local Structures in Proteins, Music and Poems

It is shown how the secondary structure of proteins, musical forms and verses of poems are approximately ruled by universal laws relying on graph coverings. In this direction, one explores the group structure of a variant of the SARS-Cov-2 spike protein and the group structure of apolipoprotein-H, passing from the primary code with amino acids to the secondary structures organizing the foldings. Then one look at the musical forms employed in the classical and contemporary periods. Finally, one investigates in much detail the group structure of a small poem in prose by Charles Baudelaire and that of the Bateau Ivre by Arthur Rimbaud.

Graph Coverings for Investigating Non Local Structures in Proteins, Music and Poems

It is shown how the secondary structure of proteins, musical forms and verses of poems are approximately ruled by universal laws relying on graph coverings. In this direction, one explores the group structure of a variant of the SARS-Cov-2 spike protein and the group structure of apolipoprotein-H, passing from the primary code with amino acids to the secondary structures organizing the foldings. Then one look at the musical forms employed in the classical and contemporary periods. Finally, one investigates in much detail the group structure of a small poem in prose by Charles Baudelaire and that of the Bateau Ivre by Arthur Rimbaud.