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Molecular insights of nickel binding to therapeutic antibodies as a possible new antibody superantigen
The binding of nickel by immune proteins can manifest as Type IV contact dermatitis (Ni-specific T cells mediated) and less frequently as Type I hypersensitivity with both mechanisms remaining unknown to date.
ReadAn Alternative HIV-1 Non-Nucleoside Reverse Transcriptase Inhibition Mechanism: Targeting the p51 Subunit
The ongoing development of drug resistance in HIV continues to push for the need of alternative drug targets in inhibiting HIV. One such target is the Reverse transcriptase (RT) enzyme which is unique and critical in the viral life cycle—a rational target that is likely to have less off-target effects in humans.
ReadEssentially Leading Antibody Production: An Investigation of Amino Acids, Myeloma, and Natural V-Region Signal Peptides in Producing Pertuzumab and Trastuzumab Variants
Boosting the production of recombinant therapeutic antibodies is crucial in both academic and industry settings. In this work, we investigated the usage of varying signal peptides by antibody V-genes and their roles in recombinant transient production, systematically comparing myeloma and the native signal peptides of both heavy and light chains in 168 antibody permutation variants.
ReadStructural modelling of the lumenal domain of human GPAA1, the metallo-peptide synthetase subunit of the transamidase complex, reveals zinc-binding mode and two flaps surrounding the active site
The transamidase complex is a molecular machine in the endoplasmic reticulum of eukaryotes that attaches a glycosylphosphatidylinositol (GPI) lipid anchor to substrate proteins after cleaving a C-terminal propeptide with a defined sequence signal. Its five subunits are very hydrophobic; thus, solubility, heterologous expression and complex reconstruction are difficult.
ReadThe Determination of HIV-1 RT Mutation Rate, Its Possible Allosteric Effects, and Its Implications on Drug Resistance
The high mutation rate of the human immunodeficiency virus type 1 (HIV-1) plays a major role in treatment resistance, from the development of vaccines to therapeutic drugs. In addressing the crux of the issue, various attempts to estimate the mutation rate of HIV-1 resulted in a large range of 10−5–10−3 errors/bp/cycle due to the use of different types of investigation methods.
ReadPerspective: The promises of a holistic view of proteins-impact on antibody engineering and drug discovery
The reductionist approach is prevalent in biomedical science. However, increasing evidence now shows that biological systems cannot be simply considered as the sum of its parts. With experimental, technological and computational advances, we can now do more than view parts in isolation, thus wepropose that an increasing holistic view (where a protein is investigated as much as a whole as possible) is now timely.
ReadAllostery Advocates in Monoclonal Antibody Engineering towards Antigen Binding
Current therapeutics antibodies, such as Trastuzumab and Pertuzumab, have marked significant success in disease treatment, particularly for Her2 positive cancers.
ReadA computational study for rational HIV-1 non-nucleoside Reverse Transcriptase inhibitor selection and the discovery of novel allosteric pockets for inhibitor design
HIV drug resistant mutations that render the current Highly Active Anti-Retroviral Therapy (HAART) cocktail drugs ineffective are increasingly reported. To study the mechanisms of these mutations in conferring drug resistance, we computationally analyzed 14 reverse transcriptase (RT) structures of HIV-1 on the following parameters: drug-binding pocket volume, allosteric effects caused by the mutations, and structural thermal stability.
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