Role of cysteine residues in hemoglobin structure and function: Transfer of p-mercuribenzoate from α subunits to β subunits during tetramer formation

8-oxoguanine glycosylase (OGG1) is a base excision repair enzyme responsible for the recognition and removal of 8-oxoguanine, a commonly occurring oxidized DNA modification. OGG1 prevents the accumulation of mutations and regulates the transcription of various oxidative stress-response genes. In addition to targeting DNA, oxidative stress can affect proteins like OGG1 itself, specifically at cysteine residues. Previous work has shown that the function of OGG1 is sensitive to oxidants, with the cysteine residues of OGG1 being the most likely site of oxidation. Due to the integral role of OGG1 in maintaining cellular homeostasis under oxidative stress, it is important to understand the effect of oxidants on OGG1 and the role of cysteines in its structure and function. In this study, we investigate the role of the cysteine residues in the function of OGG1 by mutating and characterizing each cysteine residue. Our results indicate that the cysteines in OGG1 fall into four functional categories: those that are necessary for (1) glycosylase activity (C146 and C255), (2) lyase activity (C140S, C163, C241 and C253), (3) structural stability (C253), and (4) those with no known function (C28 and C75). These results suggest that under conditions of oxidative stress, cysteine can be targeted for modifications, thus altering the response of OGG1 and affecting its downstream cellular functions.

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Faculty Opinions recommendation of Critical role of cyclophilin A and its prolyl-peptidyl isomerase activity in the structure and function of the hepatitis C virus replication complex.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1162955.623591 ◽

2009 ◽

Author(s):

Teresa Compton

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Replication ◽

Critical Role ◽

Cyclophilin A ◽

Structure And Function ◽

Replication Complex ◽

Isomerase Activity ◽

And Function

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Essential Role of Septin 7 in Skeletal Muscle Structure and Function

Biophysical Journal ◽

10.1016/j.bpj.2019.11.1500 ◽

2020 ◽

Vol 118 (3) ◽

pp. 258a

Author(s):

Laszlo Csernoch ◽

Mónika Gönczi ◽

Zsolt Ráduly ◽

László Szabó ◽

Nóra Dobrosi ◽

...

Keyword(s):

Skeletal Muscle ◽

Essential Role ◽

Structure And Function ◽

Muscle Structure ◽

And Function

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Effects of Dysbiosis and Dietary Manipulation on the Digestive Microbiota of a Detritivorous Arthropod

Microorganisms ◽

10.3390/microorganisms9010148 ◽

2021 ◽

Vol 9 (1) ◽

pp. 148

Author(s):

Marius Bredon ◽

Elisabeth Depuydt ◽

Lucas Brisson ◽

Laurent Moulin ◽

Ciriac Charles ◽

...

Keyword(s):

Crucial Role ◽

Structure And Function ◽

Ecological Interactions ◽

Dietary Manipulation ◽

Biotic Factors ◽

Abiotic And Biotic Factors ◽

And Function ◽

Multicellular Organisms ◽

Over Time

The crucial role of microbes in the evolution, development, health, and ecological interactions of multicellular organisms is now widely recognized in the holobiont concept. However, the structure and stability of microbiota are highly dependent on abiotic and biotic factors, especially in the gut, which can be colonized by transient bacteria depending on the host’s diet. We studied these impacts by manipulating the digestive microbiota of the detritivore Armadillidium vulgare and analyzing the consequences on its structure and function. Hosts were exposed to initial starvation and then were fed diets that varied the different components of lignocellulose. A total of 72 digestive microbiota were analyzed according to the type of the diet (standard or enriched in cellulose, lignin, or hemicellulose) and the period following dysbiosis. The results showed that microbiota from the hepatopancreas were very stable and resilient, while the most diverse and labile over time were found in the hindgut. Dysbiosis and selective diets may have affected the host fitness by altering the structure of the microbiota and its predicted functions. Overall, these modifications can therefore have effects not only on the holobiont, but also on the “eco-holobiont” conceptualization of macroorganisms.

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Neuroplacentology in congenital heart disease: placental connections to neurodevelopmental outcomes

Pediatric Research ◽

10.1038/s41390-021-01521-7 ◽

2021 ◽

Author(s):

Rachel L. Leon ◽

Imran N. Mir ◽

Christina L. Herrera ◽

Kavita Sharma ◽

Catherine Y. Spong ◽

...

Keyword(s):

Brain Development ◽

Congenital Heart ◽

Fetal Brain ◽

In Utero ◽

Structure And Function ◽

Brain Growth ◽

Neurodevelopmental Outcomes ◽

Fetal Brain Development ◽

And Function

Abstract Children with congenital heart disease (CHD) are living longer due to effective medical and surgical management. However, the majority have neurodevelopmental delays or disorders. The role of the placenta in fetal brain development is unclear and is the focus of an emerging field known as neuroplacentology. In this review, we summarize neurodevelopmental outcomes in CHD and their brain imaging correlates both in utero and postnatally. We review differences in the structure and function of the placenta in pregnancies complicated by fetal CHD and introduce the concept of a placental inefficiency phenotype that occurs in severe forms of fetal CHD, characterized by a myriad of pathologies. We propose that in CHD placental dysfunction contributes to decreased fetal cerebral oxygen delivery resulting in poor brain growth, brain abnormalities, and impaired neurodevelopment. We conclude the review with key areas for future research in neuroplacentology in the fetal CHD population, including (1) differences in structure and function of the CHD placenta, (2) modifiable and nonmodifiable factors that impact the hemodynamic balance between placental and cerebral circulations, (3) interventions to improve placental function and protect brain development in utero, and (4) the role of genetic and epigenetic influences on the placenta–heart–brain connection. Impact Neuroplacentology seeks to understand placental connections to fetal brain development. In fetuses with CHD, brain growth abnormalities begin in utero. Placental microstructure as well as perfusion and function are abnormal in fetal CHD.

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Endogenous Mammalian Cardiotonic Steroids—A New Cardiovascular Risk Factor?—A Mini-Review

Life ◽

10.3390/life11080727 ◽

2021 ◽

Vol 11 (8) ◽

pp. 727

Author(s):

Natalia Słabiak-Błaż ◽

Grzegorz Piecha

Keyword(s):

Adenosine Triphosphatase ◽

Therapeutic Strategies ◽

Structure And Function ◽

Sodium Potassium ◽

Sodium Homeostasis ◽

Cardiovascular Tissue ◽

Ancient Times ◽

And Function ◽

Regulation Of Blood Pressure

The role of endogenous mammalian cardiotonic steroids (CTS) in the physiology and pathophysiology of the cardiovascular system and the kidneys has interested researchers for more than 20 years. Cardiotonic steroids extracted from toads or plants, such as digitalis, have been used to treat heart disease since ancient times. CTS, also called endogenous digitalis-like factors, take part in the regulation of blood pressure and sodium homeostasis through their effects on the transport enzyme called sodium–potassium adenosine triphosphatase (Na/K-ATPase) in renal and cardiovascular tissue. In recent years, there has been increasing evidence showing deleterious effects of CTS on the structure and function of the heart, vasculature and kidneys. Understanding the role of CTS may be useful in the development of potential new therapeutic strategies.

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