Development of inhibitors as research tools for carbohydrate-processing enzymes

2012 ◽  
Vol 40 (5) ◽  
pp. 913-928 ◽  
Author(s):  
Tracey M. Gloster

Carbohydrates, which are present in all domains of life, play important roles in a host of cellular processes. These ubiquitous biomolecules form highly diverse and often complex glycan structures without the aid of a template. The carbohydrate structures are regulated solely by the location and specificity of the enzymes responsible for their synthesis and degradation. These enzymes, glycosyltransferases and glycoside hydrolases, need to be functionally well characterized in order to investigate the structure and function of glycans. The use of enzyme inhibitors, which target a particular enzyme, can significantly aid this understanding, and may also provide insights into therapeutic applications. The present article describes some of the approaches used to design and develop enzyme inhibitors as tools for investigating carbohydrate-processing enzymes.

2021 ◽  
Vol 134 (16) ◽  
Author(s):  
Robert Mahen

ABSTRACT To gain a holistic understanding of cellular function, we must understand not just the role of individual organelles, but also how multiple macromolecular assemblies function collectively. Centrioles produce fundamental cellular processes through their ability to organise cytoskeletal fibres. In addition to nucleating microtubules, centrioles form lesser-known polymers, termed rootlets. Rootlets were identified over a 100 years ago and have been documented morphologically since by electron microscopy in different eukaryotic organisms. Rootlet-knockout animals have been created in various systems, providing insight into their physiological functions. However, the precise structure and function of rootlets is still enigmatic. Here, I consider common themes of rootlet function and assembly across diverse cellular systems. I suggest that the capability of rootlets to form physical links from centrioles to other cellular structures is a general principle unifying their functions in diverse cells and serves as an example of how cellular function arises from collective organellar activity.


2011 ◽  
Vol 39 (3) ◽  
pp. 707-718 ◽  
Author(s):  
René A.W. Frank

Ionotropic receptors, including the NMDAR (N-methyl-D-aspartate receptor) mediate fast neurotransmission, neurodevelopment, neuronal excitability and learning. In the present article, the structure and function of the NMDAR is reviewed with the aim to condense our current understanding and highlight frontiers where important questions regarding the biology of this receptor remain unanswered. In the second part of the present review, new biochemical and genetic approaches for the investigation of ion channel receptor complexes will be discussed.


1976 ◽  
Vol 70 (2) ◽  
pp. 261-286 ◽  
Author(s):  
C R Kahn

Receptors for peptide hormones and neurotransmitters are integral components of the plasma membrane of cells which serve to couple the external milieu to the intracellular regulators of metabolism. These macromolecules are usually high molecular weight glycoproteins, and in many cases appear to have more than one subunit capable of binding the hormone. The interaction of the hormone or neurotransmitter with its receptor is rapid, reversible, and of high affinity and specificity. Many receptors exhibit cooperative properties in hormone binding or biological function. The concentration of receptors on the membrane is a function of continued synthesis and degradation, and may be altered by a variety of factors including the hormone itself. The fluid mosaic nature of the membrane may allow hormone receptors and effectors to exist in free floating states. Further investigations of the hormone-receptor interaction will no doubt yield new insights into both the mechanism of hormone action and membrane structure and function.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1824 ◽  
Author(s):  
Brigitte Schönberger ◽  
Christoph Schaal ◽  
Richard Schäfer ◽  
Björn Voß

Tight regulation of cellular processes is key to the development of complex organisms but also vital for simpler ones. During evolution, different regulatory systems have emerged, among them RNA-based regulation that is carried out mainly by intramolecular and intermolecular RNA–RNA interactions. However, methods for the transcriptome-wide detection of these interactions were long unavailable. Recently, three publications described high-throughput methods to directly detect RNA duplexes in living cells. This promises to enable in-depth studies of RNA-based regulation and will narrow the gaps in our understanding of RNA structure and function. In this review, we highlight the benefits of these methods and their commonalities and differences and, in particular, point to methodological shortcomings that hamper their wider application. We conclude by presenting ideas for how to overcome these problems and commenting on the prospects we see in this area of research.


2011 ◽  
Vol 286 (17) ◽  
pp. 15483-15495 ◽  
Author(s):  
Alan Cartmell ◽  
Lauren S. McKee ◽  
Maria J. Peña ◽  
Johan Larsbrink ◽  
Harry Brumer ◽  
...  

2010 ◽  
Vol 38 (4) ◽  
pp. 1105-1109 ◽  
Author(s):  
Daniela Hahn ◽  
Jean D. Beggs

RNA helicases are involved in many cellular processes. Pre-mRNA splicing requires eight different DExD/H-box RNA helicases, which facilitate spliceosome assembly and remodelling of the intricate network of RNA rearrangements that are central to the splicing process. Brr2p, one of the spliceosomal RNA helicases, stands out through its unusual domain architecture. In the present review we highlight the advances made by recent structural and biochemical studies that have important implications for the mechanism and regulation of Brr2p activity. We also discuss the involvement of human Brr2 in retinitis pigmentosa, a degenerative eye disease, and how its functions in splicing might connect to the molecular pathology of the disease.


2017 ◽  
Vol 13 (12) ◽  
pp. 2545-2550 ◽  
Author(s):  
Md. Mehedi Hasan ◽  
Dianjing Guo ◽  
Hiroyuki Kurata

Cysteine S-sulfenylation is a major type of posttranslational modification that contributes to protein structure and function regulation in many cellular processes.


2021 ◽  
Vol 22 (12) ◽  
pp. 6284
Author(s):  
Morgana K. Kellogg ◽  
Sarah C. Miller ◽  
Elena B. Tikhonova ◽  
Andrey L. Karamyshev

Signal recognition particle (SRP) is an RNA and protein complex that exists in all domains of life. It consists of one protein and one noncoding RNA in some bacteria. It is more complex in eukaryotes and consists of six proteins and one noncoding RNA in mammals. In the eukaryotic cytoplasm, SRP co-translationally targets proteins to the endoplasmic reticulum and prevents misfolding and aggregation of the secretory proteins in the cytoplasm. It was demonstrated recently that SRP also possesses an earlier unknown function, the protection of mRNAs of secretory proteins from degradation. In this review, we analyze the progress in studies of SRPs from different organisms, SRP biogenesis, its structure, and function in protein targeting and mRNA protection.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qiyin Zhou ◽  
Yawen Zheng ◽  
Yi Sun

AbstractMitochondria are the powerhouse of a cell. The structure and function of mitochondria are precisely regulated by multiple signaling pathways. Neddylation, a post-translational modification, plays a crucial role in various cellular processes including cellular metabolism via modulating the activity, function and subcellular localization of its substrates. Recently, accumulated data demonstrated that neddylation is involved in regulation of morphology, trafficking and function of mitochondria. Mechanistic elucidation of how mitochondria is modulated by neddylation would further our understanding of mitochondrial regulation to a new level. In this review, we first briefly introduce mitochondria, then neddylation cascade, and known protein substrates subjected to neddylation modification. Next, we summarize current available data of how neddylation enzymes, its substrates (including cullins/Cullin-RING E3 ligases and non-cullins) and its inhibitor MLN4924 regulate the structure and function of mitochondria. Finally, we propose the future perspectives on this emerging and exciting field of mitochondrial research.


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