scholarly journals Protein–protein interactions in “cis-AT” polyketide synthases

2018 ◽  
Vol 35 (10) ◽  
pp. 1082-1096 ◽  
Author(s):  
Greg J. Dodge ◽  
Finn P. Maloney ◽  
Janet L. Smith
Keyword(s):  
Protein Interactions ◽  
Active Site ◽  
Catalytic Domain ◽  
Polyketide Synthases ◽  
Protein Protein Interactions ◽  
P Protein ◽  
In Cis

Protein–protein interactions of cis-AT polyketide synthases are dominated by the travels of the ACP domain to the active site entrance of each catalytic domain.

scholarly journals Targeted disruption of PKC from AKAP Signaling Complexes

2021 ◽  
Author(s):  
Ameya J. Limaye ◽  
George N. Bendzunas ◽  
Eileen Kennedy
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Targeted Disruption ◽  
Physiological Processes ◽  
Kinase C ◽  
P Protein

Protein Kinase C (PKC) is a member of the AGC subfamily of kinases and regulates a wide array of signaling pathways and physiological processes. Protein-protein interactions involving PKC and its...

scholarly journals Targeting protein–protein interactions by rational design: mimicry of protein surfaces

2006 ◽  
Vol 3 (7) ◽  
pp. 215-233 ◽  
Author(s):  
Steven Fletcher ◽  
Andrew D Hamilton
Keyword(s):  
Protein Interactions ◽  
Active Site ◽  
Rational Design ◽  
Considerable Progress ◽  
Biological Processes ◽  
Protein Protein Interactions ◽  
Protein Surfaces ◽  
Enzyme Active Site ◽  
Novel Therapeutics ◽  
Interfacial Areas

Protein–protein interactions play key roles in a range of biological processes, and are therefore important targets for the design of novel therapeutics. Unlike in the design of enzyme active site inhibitors, the disruption of protein–protein interactions is far more challenging, due to such factors as the large interfacial areas involved and the relatively flat and featureless topologies of these surfaces. Nevertheless, in spite of such challenges, there has been considerable progress in recent years. In this review, we discuss this progress in the context of mimicry of protein surfaces: targeting protein–protein interactions by rational design.

scholarly journals Structure of PDE3A–SLFN12 complex and structure-based design for a potent apoptosis inducer of tumor cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Chen ◽  
Nan Liu ◽  
Yinpin Huang ◽  
Yuanxun Wang ◽  
Yuxing Sun ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Catalytic Domain ◽  
Cultured Cells ◽  
Hydrophobic Interactions ◽  
Complex Structure ◽  
Protein A ◽  
Protein Translation ◽  
Protein Protein Interactions ◽  
Cryo Electron Microscopy ◽  
Apoptosis Inducer

AbstractMolecular glues are a class of small molecular drugs that mediate protein-protein interactions, that induce either the degradation or stabilization of target protein. A structurally diverse group of chemicals, including 17-β-estradiol (E2), anagrelide, nauclefine, and DNMDP, induces apoptosis by forming complexes with phosphodiesterase 3A (PDE3A) and Schlafen 12 protein (SLFN12). They do so by binding to the PDE3A enzymatic pocket that allows the compound-bound PDE3A to recruit and stabilize SLFN12, which in turn blocks protein translation, leading to apoptosis. In this work, we report the high-resolution cryo-electron microscopy structure of PDE3A-SLFN12 complexes isolated from cultured HeLa cells pre-treated with either anagrelide, or nauclefine, or DNMDP. The PDE3A-SLFN12 complexes exhibit a butterfly-like shape, forming a heterotetramer with these small molecules, which are packed in a shallow pocket in the catalytic domain of PDE3A. The resulting small molecule-modified interface binds to the short helix (E552-I558) of SLFN12 through hydrophobic interactions, thus “gluing” the two proteins together. Based on the complex structure, we designed and synthesized analogs of anagrelide, a known drug used for the treatment of thrombocytosis, to enhance their interactions with SLFN12, and achieved superior efficacy in inducing apoptosis in cultured cells as well as in tumor xenografts.

scholarly journals Label-free methods for optical in vitro characterization of protein–protein interactions

2021 ◽  
Author(s):  
Fabian Soltermann ◽  
Weston B. Struwe ◽  
Philipp Kukura
Keyword(s):  
Protein Interactions ◽  
Label Free ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
P Protein ◽  
In Vitro Characterization ◽  
And Function

Protein–protein interactions are involved in the regulation and function of the majority of cellular processes.

scholarly journals Molecular basis for the interaction between human choline kinase alpha and the SH3 domain of the c-Src tyrosine kinase

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stefanie L. Kall ◽  
Kindra Whitlatch ◽  
Thomas E. Smithgall ◽  
Arnon Lavie
Keyword(s):  
Crystal Structures ◽  
Protein Interactions ◽  
Catalytic Domain ◽  
Sh3 Domain ◽  
Crystallographic Analysis ◽  
Choline Kinase ◽  
Protein Protein Interactions ◽  
Src Tyrosine Kinase ◽  
Patient Prognosis ◽  
Co Precipitation

AbstractCholine kinase alpha is a 457-residue protein that catalyzes the reaction between ATP and choline to yield ADP and phosphocholine. This metabolic action has been well studied because of choline kinase’s link to cancer malignancy and poor patient prognosis. As the myriad of x-ray crystal structures available for this enzyme show, chemotherapeutic drug design has centered on stopping the catalytic activity of choline kinase and reducing the downstream metabolites it produces. Furthermore, these crystal structures only reveal the catalytic domain of the protein, residues 80–457. However, recent studies provide evidence for a non-catalytic protein-binding role for choline kinase alpha. Here, we show that choline kinase alpha interacts with the SH3 domain of c-Src. Co-precipitation assays, surface plasmon resonance, and crystallographic analysis of a 1.5 Å structure demonstrate that this interaction is specific and is mediated by the poly-proline region found N-terminal to the catalytic domain of choline kinase. Taken together, these data offer strong evidence that choline kinase alpha has a heretofore underappreciated role in protein-protein interactions, which offers an exciting new way to approach drug development against this cancer-enhancing protein.

The evolutionary origin and possible functional roles of FNIII domains in two Microbacterium aurum B8.A granular starch degrading enzymes, and in other carbohydrate acting enzymes

Amylase ◽  
2017 ◽  
Vol 1 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Vincent Valk ◽  
Rachel M. van der Kaaij ◽  
Lubbert Dijkhuizen
Keyword(s):  
Protein Interactions ◽  
Catalytic Domain ◽  
Substrate Surface ◽  
Carbohydrate Binding ◽  
Protein Protein Interactions ◽  
Functional Roles ◽  
Cazy Database ◽  
Carbohydrate Binding Modules ◽  
Fibronectin Type Iii

AbstractFibronectin type III (FNIII) domains were first identified in the eukaryotic plasma protein fibronectin, where they act as structural spacers or enable protein-protein interactions. Recently we characterized two large and multi-domain amylases in Microbacterium aurum B8.A that both carry multiple FNIII and carbohydrate binding modules (CBMs). The role of (multiple) FNIII domains in such carbohydrate acting enzymes is currently unclear. Four hypothetical functions are considered here: a substrate surface disruption domain, a carbohydrate binding module, as a stable linker, or enabling protein-protein interactions. We performed a phylogenetic analysis of all FNIII domains identified in proteins listed in the CAZy database. These data clearly show that the FNIII domains in eukaryotic and archaeal CAZy proteins are of bacterial origin and also provides examples of interkingdom gene transfer from Bacteria to Archaea and Eucarya. FNIII domains occur in a wide variety of CAZy enzymes acting on many different substrates, suggesting that they have a non-specific role in these proteins. While CBM domains are mostly found at protein termini, FNIII domains are commonly located between other protein domains. FNIII domains in carbohydrate acting enzymes thus may function mainly as stable linkers to allow optimal positioning and/or flexibility of the catalytic domain and other domains, such as CBM.

Protein mixtures of environmentally friendly zein to understand protein–protein interactions through biomaterials synthesis, hemolysis, and their antimicrobial activities

2014 ◽  
Vol 16 (27) ◽  
pp. 14257-14270 ◽  
Author(s):  
Aabroo Mahal ◽  
Manoj Kumar Goshisht ◽  
Poonam Khullar ◽  
Harsh Kumar ◽  
Narinder Singh ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Environmentally Friendly ◽  
Antimicrobial Activities ◽  
Biological Applications ◽  
Protein Protein Interactions ◽  
P Protein

Protein–protein interactions through biomaterials synthesis for biological applications.

scholarly journals Stimulation of Bordetella pertussisAdenylate Cyclase Toxin Intoxication by Its Hemolysin Domain

2000 ◽  
Vol 68 (6) ◽  
pp. 3727-3730 ◽  
Author(s):  
Masaaki Iwaki ◽  
Kazunari Kamachi ◽  
Toshifumi Konda
Keyword(s):  
Adenylate Cyclase ◽  
Protein Interactions ◽  
Bordetella Pertussis ◽  
Hemolytic Activity ◽  
Cytoplasmic Membrane ◽  
Catalytic Domain ◽  
Protein Protein Interactions ◽  
Adenylate Cyclase Toxin ◽  
Stimulation Of

ABSTRACT The internalization of the N-terminal catalytic domain ofBordetella pertussis adenylate cyclase toxin (ACT) across the cytoplasmic membrane has been considered to occur independently from protein-protein interactions which can lead to oligomerization required for hemolytic activity by its C-terminal hemolysin domain. Here we report that when added in excess, this hemolysin domain stimulates the internalization, suggesting the involvement of protein-protein interactions in cell-invasive activity of ACT, as well as its hemolytic activity.

scholarly journals LncRNAs and Immunity: Coding the Immune System with Noncoding Oligonucleotides

2021 ◽  
Vol 22 (4) ◽  
pp. 1741
Author(s):  
Marco Bocchetti ◽  
Marianna Scrima ◽  
Federica Melisi ◽  
Amalia Luce ◽  
Rossella Sperlongano ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Protein Interactions ◽  
Biological Effects ◽  
Noncoding Rnas ◽  
Immune Mechanism ◽  
Protein Protein Interactions ◽  
Immune Mediated ◽  
Inflammatory Bowel ◽  
In Cis ◽  
Rna And Dna

Long noncoding RNAs (lncRNAs) represent key regulators of gene transcription during the inflammatory response. Recent findings showed lncRNAs to be dysregulated in human diseases, such as inflammatory bowel disease, diabetes, allergies, asthma, and cancer. These noncoding RNAs are crucial for immune mechanism, as they are involved in differentiation, cell migration and in the production of inflammatory mediators through regulating protein–protein interactions or their ability to assemble with RNA and DNA. The last interaction can occur in cis or trans and is responsible for all the possible lncRNAs biological effects. Our proposal is to provide an overview on lncRNAs roles and functions related to immunity and immune mediated diseases, since these elucidations could be beneficial to untangle the complex bond between them.

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