Cytosine deaminase: structural modifications studies

Structural modification studies have been shown that a cysteine, a histidine and possibly an arginine residue are involved in the catalytic process. The enzyme gave a single band on polyacrylamide gel electrophoresis, and the amino acid analysis showed it to contain a high proportion of hydrophobic residues, which was in agreement with the chemical modification results.     

Structural studies of discoidal lipoprotein A-I

Apolipoprotein A-I (apoA-I) is a major exchangeable apolipoprotein of high-density lipoproteins (HDLs), and plays an important role in reverse cholesterol transport. This process involves transport of cholesterol from peripheral tissues to the liver for processing, thereby eliminating excess cholesterol from the body. The function of apoA-I and its interaction with other components of HDL, including lecithin-cholesterol acyltransferase, seems to be closely linked to its structural plasticity. ApoA-I is likely to undergo changes in its structure and orientation between the various HDL subclasses and, therefore, knowledge of the precise structure of apoA-I is essential for understanding its role in the antiatherogenic properties of HDL. This review focuses on the role of apoA-I in reverse cholesterol transport and the work done by various groups to determine the structure of apoA-I in discoidal HDL particles.     

Cytosine modifications in neurodevelopment and diseases

DNA methylation has been studied comprehensively and linked to both normal neurodevelopment and neurological diseases. The recent identification of several new DNA modifications, including 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine, has given us a new perspective on the previously observed plasticity in 5mC-dependent regulatory processes. Here, we review the latest research into these cytosine modifications, focusing mainly on their roles in neurodevelopment and diseases.     

Structural studies of elongation and release factors

The elongation and termination steps of protein synthesis are controlled by elongation and release factors, respectively. Elongation factors deliver the aminoacyl tRNA to the ribosomal A site, ensuring the elongation of the nascent polypeptide chain by one amino acid at a time, while release factors recognize the stop codons and trigger the release of the polypeptide from the ribosome. Recently, highresolution crystal structures of ribosomes as well as translation factors on and off the ribosome have contributed a great deal to our understanding of the molecular basis of protein synthesis. This review concentrates on recent developments in our understanding of the elongation and termination steps of protein synthesis, particularly the roles of translation factors and their similarities and differences in the eukaryotic cytosol and prokaryotic systems, through a combination of structural and biochemical studies. Received 25 October 2007; received after revision 5 December 2007; accepted 7 December 2007     

Muscle adenylic deaminase

Zusammenfassung Der grössere Teil der Muskeldeaminase und Adenylsäure kann nur bei hohen Salzkonzentrationen extrahiert werden. Die Fähigkeit des Muskels für Adenyldeamination scheint grösser zu sein als seine ATP-ase-Kapazität. Beobachtungen über die Verteilung des Enzymes und seine Kinetik werden beschrieben.

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Haskell Fellow.

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Established Investigator of the American Heart Association.     

Pharmacological modification of hemoglobin F expression in sickle cell anemia: An update on hydroxyurea studies

The most studied pharmacological intervention in sickle cell anemia aiming at elevating HbF expression is the use of hydroxyurea. At the present time the experience has been that after 1 year of treatment with maximum tolerated doses (MTD) all patients showed increases of percent HbF, with a mean of 15% HbF, without apparent side effects besides the reversible ones observed during the process of attaining the MTD. The question of efficacy is presently being investigated by a multicenter placebo controlled double blind clinical trial that involves more than 20 sites. The goal of the study is to determine if hydroxyurea can decrease the incidence of painful crises by 50%. Results of this study are not expected before the end of 1993.     

Structural studies of a phosphatidyl serine-amorphous calcium phosphate complex

A phosphatidyl serine-amorphous calcium phosphate complex has been synthesized as a model of the matrix vesicle system that is associated with the induction of mineral deposition in bone, cartilage and dentine. The complex has been studied using a novel technique of subtractive extended X-ray absorption fine structure (EXAFS). This enables spectra of the components of the molecules to be subtracted from the complex so as to identify the sites of interaction. The results suggest there is a movement in the nitrogen atom of the phosphatidyl serine which approaches the calcium atom in the mineral phase. This interpretation would link the membrane structure of the vesicle to the structure of the mineral in a way that could explain some of its roles in biomineralization. Received 14 November 1997; accepted 23 December 1997     

Guinea pig liver cytosol has an L-threonine deaminase activity distinct from L-serine deaminase]

Using sodium sulfate precipitation, "Sephadex G200" gel filtration and polyacrylamide gel electrophoresis, a L-threonine desaminase was demonstrated in the Guinea-Pig liver cytosol. This enzyme was separated from the guinea pig liver L-serine desaminase possessing an auxiliary activity on L-threonine substrate described by us in a previous work. The optimals for pH (7,1) and temperature (+ 55 degrees C) and the apparent molecular weight (134,000 + 20,000) were established.     

Human adenosine deaminase and chromosome 20

Summary In patients exhibiting in marrow cells deletion of the long arm of chromosome 20, the specific activities of adenosine deaminase in cells of the peripheral blood are normal. This suggests that the gene for adenosine deaminase is not localized to the distal segment of the long arm of this chromosome.This work was supported by Grants from the National Health and Medical Research Council of Australia and the Anti-Cancer Council of Victoria.     

AMP deaminase, 5'-nucleotidase and adenosine deaminase in rat myocardial tissue in myocardial infarction and hypothermia

AMP deaminase, 5'-nucleotidase and adenosine deaminase have been estimated in skeletal muscle and myocardial tissue in normal rats and in rats subjected to experimental myocardial infarction or hypothermia. A difference in the enzyme distribution was found between the right and left ventricles in the normal rat. A decrease in the activity of 5'-nucleotidase and an increase in the activity of adenosine deaminase were observed in infarcted myocardial tissue. The activity of all 3 enzymes was found to be depressed in the myocardium in rats subjected to hypothermia. These results are discussed in relation to adenosine production and its beneficial effects.     

Laminin: loss-of-function studies

Laminin, one of the most widely expressed extracellular matrix proteins, exerts many important functions in multiple organs/systems and at various developmental stages. Although its critical roles in embryonic development have been demonstrated, laminin’s functions at later stages remain largely unknown, mainly due to its intrinsic complexity and lack of research tools (most laminin mutants are embryonic lethal). With the advance of genetic and molecular techniques, many new laminin mutants have been generated recently. These new mutants usually have a longer lifespan and show previously unidentified phenotypes. Not only do these studies suggest novel functions of laminin, but also they provide invaluable animal models that allow investigation of laminin’s functions at late stages. Here, I first briefly introduce the nomenclature, structure, and biochemistry of laminin in general. Next, all the loss-of-function mutants/models for each laminin chain are discussed and their phenotypes compared. I hope to provide a comprehensive review on laminin functions and its loss-of-function models, which could serve as a reference for future research in this understudied field.     

On the mechanism of the cation- and substrate analog-activated enzyme reaction: Glucosamine-6-phosphate deaminase

Zusammenfassung Die Reaktion der Glukosamin-6-Phosphat-Deaminase, an der Metallionen und ein Substratanalogon teilnehmen, wurde vom mechanistischen Standpunkt aus bearbeitet und auf der Basis der Komplexierung desES-Komplexes mit den obengenannten Aktivatoren dargestellt.     

Occurrence of sepiapterin deaminase in the silkworm,Bombyx mori

Zusammenfassung Im Seidenspinner (Bombyx mori) wird ein Enzym nachgewiesen und angereichert, welches das gelbe Pigment Sepiapterin zu Xanthopterin-B₂ desaminiert. Ferner wird die Substratspezifität des Enzympräparates abgeklärt.     

Protein arginine methylation: a prominent modification and its demethylation

Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues. The reversibility of histone modifications is an essential feature of epigenetic regulation to respond to changes in environmental factors, signalling events, or metabolic alterations. Prominent histone modifications like lysine acetylation and lysine methylation are reversible. Enzyme family pairs have been identified, with each pair of lysine acetyltransferases/deacetylases and lysine methyltransferases/demethylases operating complementarily to generate or erase lysine modifications. Several analyses also indicate a reversible nature of arginine methylation, but the enzymes facilitating direct removal of methyl moieties from arginine residues in proteins have been discussed controversially. Differing reports have been seen for initially characterized putative candidates, like peptidyl arginine deiminase 4 or Jumonji-domain containing protein 6. Here, we review the most recent cellular, biochemical, and mass spectrometry work on arginine methylation and its reversible nature with a special focus on putative arginine demethylases, including the enzyme superfamily of Fe(II) and 2-oxoglutarate-dependent oxygenases.