475 results match your criteria Advances in Protein Chemistry and Structural Biology[Journal]


Accelerating therapeutic protein design.

Adv Protein Chem Struct Biol 2022 2;130:85-118. Epub 2022 Mar 2.

University Hospital Tübingen, Division of Translational Oncology, Tübingen, Germany; Max Planck Institute for Biology, Tübingen, Germany. Electronic address:

Protein structures provide for defined microenvironments that can support complex pharmacological functions, otherwise unachievable by small molecules. The advent of therapeutic proteins has thus greatly broadened the range of manageable disorders. Leveraging the knowledge and recent advances in de novo protein design methods has the prospect of revolutionizing how protein drugs are discovered and developed. Read More

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Structure and chemistry of enzymatic active sites that play a role in the switch and conformation mechanism.

Adv Protein Chem Struct Biol 2022 14;130:59-83. Epub 2022 Mar 14.

Computer Aided Drug Design and Molecular Modelling Lab, Department of Bioinformatics, Science Block, Alagappa University, Karaikudi, Tamil Nadu, India. Electronic address:

Enzymes, which are biological molecules, are constructed from polypeptide chains, and these molecules are activated through reaction mechanisms. It is the role of enzymes to speed up chemical reactions that are used to build or break down cell structures. Activation energy is reduced by the enzymes' selective binding of substrates in a protected environment. Read More

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Evolutionary aspect of Miltefosine transporter proteins in Leishmania major.

Adv Protein Chem Struct Biol 2022 25;130:399-418. Epub 2022 Feb 25.

National Centre for Cell Science, NCCS Complex, SP Pune University Campus, Pune, India. Electronic address:

Transporter proteins, P-glycoprotein (P-gp) and P4ATPase-CDC50, are responsible for the transport of Miltefosine drug across cell membrane of a protozoan parasite Leishmania major. Mutations or change in activity of these proteins may lead to emergence of resistance in the parasite. Owing to the structural and functional importance of these transporter proteins, we have tried to decipher the evolutionary divergence of these Miltefosine transporter proteins across different forms of life including Protists, Fungi, Plants and Animals. Read More

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February 2022

Computational prediction of protein functional sites-Applications in biotechnology and biomedicine.

Authors:
Florencio Pazos

Adv Protein Chem Struct Biol 2022 17;130:39-57. Epub 2022 Jan 17.

Computational Systems Biology Group, National Center for Biotechnology (CNB-CSIC), Madrid, Spain. Electronic address:

There are many computational approaches for predicting protein functional sites based on different sequence and structural features. These methods are essential to cope with the sequence deluge that is filling databases with uncharacterized protein sequences. They complement the more expensive and time-consuming experimental approaches by pointing them to possible candidate positions. Read More

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January 2022

Computational structural assessment of BReast CAncer type 1 susceptibility protein (BRCA1) and BRCA1-Associated Ring Domain protein 1 (BARD1) mutations on the protein-protein interface.

Adv Protein Chem Struct Biol 2022 21;130:375-397. Epub 2022 Apr 21.

Department of Biomedical Sciences, College of Health and Sciences, QU Health, Qatar University, Doha, Qatar. Electronic address:

Breast cancer type 1 susceptibility protein (BRCA1) is closely related to the BRCA2 (breast cancer type 2 susceptibility protein) and BARD1 (BRCA1-associated RING domain-1) proteins. The homodimers were formed through their RING fingers; however they form more compact heterodimers preferentially, influencing BRCA1 residues 1-109 and BARD1 residues 26-119. We implemented an integrative computational pipeline to screen all the mutations in BRCA1 and identify the most significant mutations influencing the Protein-Protein Interactions (PPI) in the BRCA1-BARD1 protein complex. Read More

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Mutations in G6PC2 gene with increased risk for development of type 2 diabetes: Understanding via computational approach.

Adv Protein Chem Struct Biol 2022 8;130:351-373. Epub 2022 Apr 8.

Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India. Electronic address:

An increase in the fast blood glucose (FBG) levels has been linked to an increased risk of developing a chronic condition, type 2 diabetes (T2D). The mutation in the G6PC2 gene was identified to have a lead role in the modulation of FBG levels. The abnormal regulation of this enzyme influences glucose-stimulated insulin secretion (GSIS), which controls the insulin levels corresponding to the system's glucose level. Read More

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Immunosafe(r)-by-design nanoparticles: Molecular targets and cell signaling pathways in a next-generation model proxy for humans.

Adv Protein Chem Struct Biol 2022 16;130:325-350. Epub 2022 Feb 16.

Consiglio Nazionale delle Ricerche, Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Palermo, Italy.

Nanotechnology research covers a wide field of studies pointing to design and shape complex matter in a scale between 1 and 100nm, with unique size-depending properties and applications. The value and potential of engineered nanoparticles in human diagnostics and therapies essentially relay on their safety and biocompatibility. Entering a cell, in fact, these particles take complex interactions with the surrounding biological environment, dramatically changing their own identity. Read More

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Recent advances in structural studies of 14-3-3 protein complexes.

Adv Protein Chem Struct Biol 2022 9;130:289-324. Epub 2022 Feb 9.

A.N. Bach Institute of Biochemistry, Federal Research Center "Fundamentals of Biotechnology" of the Russian Academy of Sciences, Moscow, Russian Federation. Electronic address:

Being phosphopeptide-binding hubs, 14-3-3 proteins coordinate multiple cellular processes in eukaryotes, including the regulation of apoptosis, cell cycle, ion channels trafficking, transcription, signal transduction, and hormone biosynthesis. Forming constitutive α-helical dimers, 14-3-3 proteins predominantly recognize specifically phosphorylated Ser/Thr sites within their partners; this generally stabilizes phosphotarget conformation and affects its activity, intracellular distribution, dephosphorylation, degradation and interactions with other proteins. Not surprisingly, 14-3-3 complexes are involved in the development of a range of diseases and are considered promising drug targets. Read More

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Designing synthetic transcription factors: A structural perspective.

Adv Protein Chem Struct Biol 2022 29;130:245-287. Epub 2022 Jan 29.

Department of Life Sciences, Presidency University, Kolkata, West Bengal, India. Electronic address:

In this chapter, we discuss different design strategies of synthetic proteins, especially synthetic transcription factors. Design and engineering of synthetic transcription factors is particularly relevant for the need-based manipulation of gene expression. With recent advances in structural biology techniques and with the emergence of other precision biochemical/physical tools, accurate knowledge on structure-function relations is increasingly becoming available. Read More

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The structural basis of histone modifying enzyme specificity and promiscuity: Implications for metabolic regulation and drug design.

Adv Protein Chem Struct Biol 2022 17;130:189-243. Epub 2022 Mar 17.

Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS, United States.

Histone modifying enzymes regulate chromatin architecture through covalent modifications and ultimately control multiple aspects of cellular function. Disruption of histone modification leads to changes in gene expression profiles and may lead to disease. Both small molecule inhibitors and intermediary metabolites have been shown to modulate histone modifying enzyme activity although our ability to identify successful drug candidates or novel metabolic regulators of these enzymes has been limited. Read More

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Understanding binding affinity and specificity of modular protein domains: A focus in ligand design for the polyproline-binding families.

Adv Protein Chem Struct Biol 2022 10;130:161-188. Epub 2022 Jan 10.

Departamento de Química Física e Instituto de Biotecnología, Facultad de Ciencias, Universidad de Granada, Granada, Spain.

Within the modular protein domains there are five families that recognize proline-rich sequences: SH3, WW, EVH1, GYF and UEV domains. This chapter reviews the main strategies developed for the design of ligands for these families, including peptides, peptidomimetics and drugs. We also describe some studies aimed to understand the molecular reasons responsible for the intrinsic affinity and specificity of these domains. Read More

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Aromatic interactions directing peptide nano-assembly.

Adv Protein Chem Struct Biol 2022 16;130:119-160. Epub 2022 Feb 16.

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India. Electronic address:

Self-assembly is a process of spontaneous organization of molecules as a result of non-covalent interactions. Organized self-assembly at the nano level is emerging as a powerful tool in the bottom-up fabrication of functional nanostructures for targeted applications. Aromatic π-π stacking plays a significant role by facilitating the persistent supramolecular association of individual subunits to the self-assembled structures of high stability. Read More

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Algorithms for protein design.

Authors:
Sekhar Talluri

Adv Protein Chem Struct Biol 2022 2;130:1-38. Epub 2022 Mar 2.

Department of Biotechnology, GITAM, Visakhapatnam, India. Electronic address:

Computational Protein Design has the potential to contribute to major advances in enzyme technology, vaccine design, receptor-ligand engineering, biomaterials, nanosensors, and synthetic biology. Although Protein Design is a challenging problem, proteins can be designed by experts in Protein Design, as well as by non-experts whose primary interests are in the applications of Protein Design. The increased accessibility of Protein Design technology is attributable to the accumulated knowledge and experience with Protein Design as well as to the availability of software and online resources. Read More

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Natural killer cell-based strategies for immunotherapy of cancer.

Adv Protein Chem Struct Biol 2022 4;129:91-133. Epub 2022 Mar 4.

Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic.

Natural killer (NK) cells are a family of lymphocytes with a natural ability to kill infected, harmed, or malignantly transformed cells. As these cells are part of the innate immunity, the cytotoxic mechanisms are activated upon recognizing specific patterns without prior antigen sensitization. This recognition is crucial for NK cell function in the maintenance of homeostasis and immunosurveillance. Read More

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Immunotherapeutic approaches for HPV-caused cervical cancer.

Adv Protein Chem Struct Biol 2022 23;129:51-90. Epub 2021 Dec 23.

Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Cervical cancer, the fourth most frequent women cancer worldwide, is mostly (about 99%) associated with human papillomavirus (HPV). Despite availability of three effective prophylactic vaccines for more than one decade and some other preventive measures, it is still the fourth cause of cancer death among women globally. Thus, development of therapeutic vaccines seems essential, which has been vastly studied using different vaccine platforms. Read More

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Antivenom: An immunotherapy for the treatment of snakebite envenoming in sub-Saharan Africa.

Adv Protein Chem Struct Biol 2022 28;129:435-477. Epub 2021 Dec 28.

School of Bioscience, Cardiff University, Cardiff, United Kingdom.

Snakebite envenoming (SBE) leads to significant morbidity and mortality, resulting in over 90,000 deaths and approximately 400,000 amputations annually. In sub-Saharan Africa (SSA) alone, SBE accounts for over 30,000 deaths per annum. Since 2017, SBE has been classified as a priority Neglected Tropical Disease (NTD) by the World Health Organisation (WHO). Read More

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Immunotherapeutic interventions in Parkinson's disease: Focus on α-Synuclein.

Adv Protein Chem Struct Biol 2022 28;129:381-433. Epub 2021 Dec 28.

Department of Biotechnology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to be University), Mullana, India. Electronic address:

Parkinson's disease (PD) is a neurodegenerative disorder characterized classically by motor manifestations. However, nonmotor symptoms appear early in the course of the disease progression, making both diagnosis and treatment difficult. The pathology of PD is complicated by the accumulation and aggregation of misfolded proteins in intracellular cytoplasmic inclusions called Lewy bodies (LBs). Read More

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Understanding the activating mechanism of the immune system against COVID-19 by Traditional Indian Medicine: Network pharmacology approach.

Adv Protein Chem Struct Biol 2022 29;129:275-379. Epub 2022 Jan 29.

School of BioSciences and Technology, Vellore Institute of Technology, Vellore, TN, India. Electronic address:

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions are occurring rapidly; it is raising the alarm around the globe. Though vaccines are currently available, the evolution and mutations in the SARS-CoV-2 threaten available vaccines' significance. The drugs are still undergoing clinical trials, and certain medications are approved for "emergency use" or as an "off-label" drug during the pandemic. Read More

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A computational model revealing the immune-related hub genes and key pathways involved in rheumatoid arthritis (RA).

Adv Protein Chem Struct Biol 2022 8;129:247-273. Epub 2022 Feb 8.

School of Biosciences and Technology, Vellore Institute of Technology, Vellore, TN, India. Electronic address:

Rheumatoid arthritis (RA) has one of the highest disability rates among inflammatory joint disorders. However, the reason and possible molecular events are still unclear. There are various treatment options available, but no complete cure. Read More

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Clostridioides difficile: Current overview and future perspectives.

Adv Protein Chem Struct Biol 2022 7;129:215-245. Epub 2022 Jan 7.

Toxins Group, National Infection Service, Public Health England, Porton Down, United Kingdom.

The most common world-wide cause of antibiotic-associated infectious diarrhea and colitis is the toxin producing bacterium, Clostridioides difficile (C. difficile). Here we review the background and characteristics of the bacterium and the toxins produced together with the epidemiology and the complex pathogenesis that leads to a broad clinical spectrum of disease. Read More

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CoVaccine HT™ adjuvant is superior to Freund's in eliciting ovine polyclonal antibodies against human tumor necrosis factor-alpha.

Adv Protein Chem Struct Biol 2022 16;129:189-213. Epub 2022 Feb 16.

Department of Biomedical Sciences, Cardiff Metropolitan University, Cardiff, United Kingdom.

Introduction: Passive immunotherapy using polyclonal antibodies plays an important role in preventing and treating antigenic and pathogenic diseases. Polyclonal antibodies are used for therapeutic, diagnostic and investigational purposes, with adjuvants employed to enhance the immune response against proteins that are poorly antigenic or self-antigens. This study aimed to optimize current immunization methods by evaluating the novel adjuvant CoVaccine HT™ against the established Freund's at producing ovine polyclonal antibodies against pro-inflammatory cytokine human recombinant tumor necrosis factor alpha (TNF-α). Read More

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Immunological insights of selectins in human disease mechanism.

Adv Protein Chem Struct Biol 2022 28;129:163-188. Epub 2022 Jan 28.

Computer Aided Drug Design and Molecular Modelling Lab, Department of Bioinformatics, Science Block, Alagappa University, Karaikudi, India. Electronic address:

Selectin enzymes are glycoproteins and are an important adhesion molecule in the mammalian immune system, especially in the inflammatory response and the healing process of tissues. Selectins play an important role in a variety of biological processes, including the rolling of leukocytes in endothelial cells, a process known as the adhesion cascade. It has recently been discovered and reported that the selectin mechanism plays a role in cancer and thrombosis disease. Read More

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Noncoding RNAs as novel immunotherapeutic tools against cancer.

Adv Protein Chem Struct Biol 2022 11;129:135-161. Epub 2022 Jan 11.

Department of Biochemistry, PostGraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:

Immunotherapy is implemented as an important treatment strategy in various malignancies. In cancer, immunotherapy is employed for successful killing of tumor cells with high specificity and greater efficacy, with minimum side effects. Despite various available strategies, cellular immunotherapy including innate (NK cells, macrophages, dendritic cells) and adaptive (B cells and T cells) immune cells plays a critical role in tumor microenvironment. Read More

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In silico tools and databases for designing cancer immunotherapy.

Adv Protein Chem Struct Biol 2022 23;129:1-50. Epub 2021 Dec 23.

Department of Computational Biology, Indraprastha Institute of Information Technology, Okhla Phase 3, New Delhi, India. Electronic address:

Immunotherapy is a rapidly growing therapy for cancer which have numerous benefits over conventional treatments like surgery, chemotherapy, and radiation. Overall survival of cancer patients has improved significantly due to the use of immunotherapy. It acts as a novel pillar for treating different malignancies from their primary to the metastatic stage. Read More

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Pore formation by pore forming membrane proteins towards infections.

Adv Protein Chem Struct Biol 2022 19;128:79-111. Epub 2021 Oct 19.

Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India. Electronic address:

Over the last 25 years, the biology of membrane proteins, including the PFPs-membranes interactions is seeking attention for the development of successful drug molecules against a number of infectious diseases. Pore forming toxins (PFTs), the largest family of PFPs are considered as a group of virulence factors produced in a large number of pathogenic systems which include streptococcus, pneumonia, Staphylococcus aureus, E. coli, Mycobacterium tuberculosis, group A and B streptococci, Corynebacterium diphtheria and many more. Read More

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January 2022

Dendritic spine membrane proteome and its alterations in autistic spectrum disorder.

Adv Protein Chem Struct Biol 2022 23;128:435-474. Epub 2021 Oct 23.

Instituto de Investigaciones Biomédicas (BIOMED), UCA-CONICET, Buenos Aires, Argentina. Electronic address:

Dendritic spines are small protrusions stemming from the dendritic shaft that constitute the primary specialization for receiving and processing excitatory neurotransmission in brain synapses. The disruption of dendritic spine function in several neurological and neuropsychiatric diseases leads to severe information-processing deficits with impairments in neuronal connectivity and plasticity. Spine dysregulation is usually accompanied by morphological alterations to spine shape, size and/or number that may occur at early pathophysiological stages and not necessarily be reflected in clinical manifestations. Read More

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January 2022

The role of membranes in function and dysfunction of intrinsically disordered amyloidogenic proteins.

Adv Protein Chem Struct Biol 2022 5;128:397-434. Epub 2021 Nov 5.

Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India. Electronic address:

Membrane-protein interactions play a major role in human physiology as well as in diseases pathology. Interaction of a protein with the membrane was previously thought to be dependent on well-defined three-dimensional structure of the protein. In recent decades, however, it has become evident that a large fraction of the proteome, particularly in eukaryotes, stays disordered in solution and these proteins are termed as intrinsically disordered proteins (IDPs). Read More

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January 2022

Molecular determinants of GPCR pharmacogenetics: Deconstructing the population variants in β-adrenergic receptor.

Adv Protein Chem Struct Biol 2022 13;128:361-396. Epub 2021 Oct 13.

CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India. Electronic address:

G protein-coupled receptors (GPCRs) are membrane proteins that play a central role in cell signaling and constitute one of the largest classes of drug targets. The molecular mechanisms underlying GPCR function have been characterized by several experimental and computational methods and provide an understanding of their role in physiology and disease. Population variants arising from nsSNPs affect the native function of GPCRs and have been implicated in differential drug response. Read More

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January 2022

Modulation of host cellular responses by gram-negative bacterial porins.

Adv Protein Chem Struct Biol 2022 30;128:35-77. Epub 2021 Oct 30.

Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, Punjab, India. Electronic address:

The outer membrane of a gram-negative bacteria encapsulates the plasma membrane thereby protecting it from the harsh external environment. This membrane acts as a sieving barrier due to the presence of special membrane-spanning proteins called "porins." These porins are β-barrel channel proteins that allow the passive transport of hydrophilic molecules and are impermeable to large and charged molecules. Read More

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January 2022

Development of enhanced conformational sampling methods to probe the activation landscape of GPCRs.

Adv Protein Chem Struct Biol 2022 20;128:325-359. Epub 2021 Dec 20.

Department of Chemistry and Biochemistry, California State University, Northridge, CA, United States.

G protein-coupled receptors (GPCRs) make up the largest superfamily of integral membrane proteins and play critical signal transduction roles in many physiological processes. Developments in molecular biology, biophysical, biochemical, pharmacological, and computational techniques aimed at these important therapeutic targets are beginning to provide unprecedented details on the structural as well as functional basis of their pleiotropic signaling mediated by G proteins, β arrestins, and other transducers. This pleiotropy presents a pharmacological challenge as the same ligand-receptor interaction can cause a therapeutic effect as well as an undesirable on-target side-effect through different downstream pathways. Read More

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January 2022