A new insight into protein-protein interactions and the effect of conformational alterations in PCNA

2020 ◽  
Vol 148 ◽  
pp. 999-1009 ◽  
Author(s):  
Vijay Kumar Bhardwaj ◽  
Rituraj Purohit
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Insight Into

scholarly journals Getting into position: the catalytic mechanisms of protein ubiquitylation

2004 ◽  
Vol 379 (3) ◽  
pp. 513-525 ◽  
Author(s):  
Lori A. PASSMORE ◽  
David BARFORD
Keyword(s):  
Protein Interactions ◽  
Regulatory Elements ◽  
Substrate Selection ◽  
Protein Protein Interactions ◽  
Different Types ◽  
Catalytic Mechanisms ◽  
Cellular Pathways ◽  
Ubiquitin Conjugating Enzymes ◽  
Insight Into

The role of protein ubiquitylation in the control of diverse cellular pathways has recently gained widespread attention. Ubiquitylation not only directs the targeted destruction of tagged proteins by the 26 S proteasome, but it also modulates protein activities, protein–protein interactions and subcellular localization. An understanding of the components involved in protein ubiquitylation (E1s, E2s and E3s) is essential to understand how specificity and regulation are conferred upon these pathways. Much of what we know about the catalytic mechanisms of protein ubiquitylation comes from structural studies of the proteins involved in this process. Indeed, structures of ubiquitin-activating enzymes (E1s) and ubiquitin-conjugating enzymes (E2s) have provided insight into their mechanistic details. E3s (ubiquitin ligases) contain most of the substrate specificity and regulatory elements required for protein ubiquitylation. Although several E3 structures are available, the specific mechanistic role of E3s is still unclear. This review will discuss the different types of ubiquitin signals and how they are generated. Recent advances in the field of protein ubiquitylation will be examined, including the mechanisms of E1, E2 and E3. In particular, we discuss the complexity of molecular recognition required to impose selectivity on substrate selection and topology of poly-ubiquitin chains.

scholarly journals MiRNA-Regulated Pathways for Hypertrophic Cardiomyopathy: Network-Based Approach to Insight into Pathogenesis

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 2016
Author(s):  
German Osmak ◽  
Natalia Baulina ◽  
Ivan Kiselev ◽  
Olga Favorova
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Signaling Pathways ◽  
Protein Interactions ◽  
Target Gene ◽  
High Throughput Sequencing ◽  
Point Of View ◽  
Specific Gene ◽  
Protein Protein Interactions ◽  
Insight Into ◽  
Sarcomeric Genes

Hypertrophic cardiomyopathy (HCM) is the most common hereditary heart disease. The wide spread of high-throughput sequencing casts doubt on its monogenic nature, suggesting the presence of mechanisms of HCM development independent from mutations in sarcomeric genes. From this point of view, HCM may arise from the interactions of several HCM-associated genes, and from disturbance of regulation of their expression. We developed a bioinformatic workflow to study the involvement of signaling pathways in HCM development through analyzing data on human heart-specific gene expression, miRNA-target gene interactions, and protein–protein interactions, available in open databases. Genes regulated by a pool of miRNAs contributing to human cardiac hypertrophy, namely hsa-miR-1-3p, hsa-miR-19b-3p, hsa-miR-21-5p, hsa-miR-29a-3p, hsa-miR-93-5p, hsa-miR-133a-3p, hsa-miR-155-5p, hsa-miR-199a-3p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-451a, and hsa-miR-497-5p, were considered. As a result, we pinpointed a module of TGFβ-mediated SMAD signaling pathways, enriched by targets of the selected miRNAs, that may contribute to the cardiac remodeling in HCM. We suggest that the developed network-based approach could be useful in providing a more accurate glimpse on pathological processes in the disease pathogenesis.

Self-diffusion of a highly concentrated monoclonal antibody by fluorescence correlation spectroscopy: insight into protein–protein interactions and self-association

Soft Matter ◽  
2019 ◽  
Vol 15 (33) ◽  
pp. 6660-6676 ◽  
Author(s):  
Jessica J. Hung ◽  
Wade F. Zeno ◽  
Amjad A. Chowdhury ◽  
Barton J. Dear ◽  
Kishan Ramachandran ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Protein Interactions ◽  
Fluorescence Correlation Spectroscopy ◽  
Correlation Spectroscopy ◽  
Protein Protein Interactions ◽  
Fluorescence Correlation ◽  
Self Diffusion ◽  
Self Association ◽  
Insight Into

Measurement and interpretation of self-diffusion of a highly concentrated mAb with different formulations in context of viscosity and protein self-interactions.

scholarly journals Occurrence of the d-Proline Chemotype in Enzyme Inhibitors

Symmetry ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 558 ◽  
Author(s):  
Elena Lenci ◽  
Andrea Trabocchi
Keyword(s):  
Amino Acids ◽  
Protein Interactions ◽  
Medicinal Chemistry ◽  
Enzyme Inhibitors ◽  
Proteolytic Enzymes ◽  
Building Blocks ◽  
Protein Protein Interactions ◽  
Conformationally Constrained ◽  
Biological Outcomes ◽  
Insight Into

Natural and nonnatural amino acids represent important building blocks for the development of peptidomimetic scaffolds, especially for targeting proteolytic enzymes and for addressing protein–protein interactions. Among all the different amino acids derivatives, proline is particularly relevant in chemical biology and medicinal chemistry due to its secondary structure’s inducing and stabilizing properties. Also, the pyrrolidine ring is a conformationally constrained template that can direct appendages into specific clefts of the enzyme binding site. Thus, many papers have appeared in the literature focusing on the use of proline and its derivatives as scaffolds for medicinal chemistry applications. In this review paper, an insight into the different biological outcomes of d-proline and l-proline in enzyme inhibitors is presented, especially when associated with matrix metalloprotease and metallo-β-lactamase enzymes.

scholarly journals Structure of the Q237W mutant of HhaI DNA methyltransferase: an insight into protein-protein interactions

2004 ◽  
Vol 385 (13) ◽  
pp. 373-379 ◽  
Author(s):  
A. Dong ◽  
L. Zhou ◽  
X. Zhang ◽  
S. Stickel ◽  
R.J. Roberts ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Dna Methyltransferase ◽  
Protein Protein Interactions ◽  
Insight Into

Can stem bromelain, a pineapple waste product, be used as a drug alternative? A mechanistic insight into protein–protein interactions

2020 ◽  
Vol 44 (45) ◽  
pp. 19450-19458
Author(s):  
Samima Khatun ◽  
Anamika Sindhu ◽  
Pannuru Venkatesu
Keyword(s):  
Bovine Serum Albumin ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Waste Product ◽  
Protein Protein Interactions ◽  
Pineapple Waste ◽  
Mechanistic Insight ◽  
Biophysical Techniques ◽  
Stem Bromelain ◽  
Insight Into

Binding of stem bromelain to bovine serum albumin induced conformational changes, as shown by various biophysical techniques.

scholarly journals Dissection of the Spindle Assembly Checkpoint by Proximity Proteomics

2020 ◽  
Author(s):  
Yenni A. Garcia ◽  
Erick F. Velasquez ◽  
Lucy W. Gao ◽  
Keith Cheung ◽  
Kevin M. Clutario ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Spindle Assembly Checkpoint ◽  
Protein Complexes ◽  
Spindle Assembly ◽  
Protein Protein Interactions ◽  
Proteomic Approach ◽  
Multiple Protein ◽  
Spatio Temporal ◽  
Insight Into

SUMMARYThe spindle assembly checkpoint (SAC) is critical for sensing defective microtubule-kinetochore attachments and tension across the kinetochore and functions to arrest cells in prometaphase to allow time to repair any errors prior to proceeding into anaphase. The SAC has a central role in ensuring the fidelity of chromosome segregation and its dysregulation has been linked to the development of human diseases like cancer. The establishment and maintenance of the SAC relies on multiple protein complexes that are intricately regulated in a spatial and temporal manner through posttranslational modifications like phosphorylation. Over the past few decades the SAC has been highly investigated and much has been learned about its protein constituents and the pathways and factors that regulate its activity. However, the spatio-temporal proximity associations of the core SAC components have not been explored in a systematic manner. Here, we have taken a BioID2 proximity-labeling proteomic approach to define the proximity protein environment for each of the five core SAC proteins BUB1, BUB3, BUBR1, MAD1L1, and MAD2L1 under conditions where the SAC is active in prometaphase. These five protein association maps were integrated to generate the SAC proximity protein network that contains multiple layers of information related to core SAC protein complexes, protein-protein interactions, and proximity associations. Our analysis validated many of the known SAC complexes and protein-protein interactions. Additionally, it uncovered new protein associations that lend insight into the functioning of the SAC and highlighted future areas that should be investigated to generate a comprehensive understanding of the SAC.

scholarly journals Mechanistic insight into light-dependent recognition of Timeless by Drosophila cryptochrome

2021 ◽  
Author(s):  
Changfan Lin ◽  
Connor M. Schneps ◽  
Siddarth Chandrasekaran ◽  
Abir Ganguly ◽  
Brian R. Crane
Keyword(s):  
Molecular Dynamics ◽  
Western Blot ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Esr Spectroscopy ◽  
Redox State ◽  
Protein Protein Interactions ◽  
Mechanistic Insight ◽  
Dynamics Simulations ◽  
Insight Into

SUMMARYCryptochrome (CRY) entrains the fly circadian clock by binding to Timeless (TIM) in light and triggering its degradation. Undocking of a helical C-terminal tail (CTT) in response to photoreduction of the CRY flavin cofactor gates TIM binding. A generally-applicable Select Western-blot-Free Tagged-protein Interaction (SWFTI) assay enables quantification of CRY binding to TIM in dark and light. The assay is utilized to study CRY variants with residue substitutions in the flavin pocket and correlate their TIM affinities with CTT undocking, as measured by pulse-dipolar ESR spectroscopy and evaluated by molecular dynamics simulations. CRY variants with the CTT removed or undocked bind TIM constitutively, whereas those incapable of photoreduction bind TIM weakly. In response to flavin redox state, two conserved histidine residues contribute to a robust on/off switch by mediating CTT interactions with the flavin pocket and TIM. Our approach provides an expeditious means to quantify protein-protein interactions and photoreceptor targeting.

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