Showing papers in "Critical Reviews in Biochemistry and Molecular Biology in 1995"

The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.

Abstract: The glutathione S-transferases (GST) represent a major group of detoxification enzymes. All eukaryotic species possess multiple cytosolic and membrane-bound GST isoenzymes, each of which displays distinct catalytic as well as noncatalytic binding properties: the cytosolic enzymes are encoded by at least five distantly related gene families (designated class alpha, mu, pi, sigma, and theta GST), whereas the membrane-bound enzymes, microsomal GST and leukotriene C, synthetase, are encoded by single genes and both have arisen separately from the soluble GST. Evidence suggests that the level of expression of GST is a crucial factor in determining the sensitivity of cells to a broad spectrum of toxic chemicals. In this article the biochemical functions of GST are described to show how individual isoenzymes contribute to resistance to carcinogens, antitumor drugs, environmental pollutants, and products of oxidative stress.A description of the mechanisms of transcriptional and posttranscriptional regulat...

The Use and Misuse of FTIR Spectroscopy in the Determination of Protein Structure

Abstract: Fourier transform infrartd (FTIR) spectroscopy is an established tool for the structural character- ization of proteins. However, many potential pitfalls exist for the unwary investigator. In this review we critically assess the application of FIlR spectroscopy to the determination of protein structure by (1) outlining the principles underlying protein secondary structure determination by FZZR spectroscopy. (2) highhghting the situations in which FZZR spectroscopy should be considered the technique of choice, (3) discussing the manner in which experiments should be conducted to derive as much physiologically relevant information as possible, and (4) outlining current methods for the determination of secondary structure from infrared spectm of proteins,

Prediction of protein structural classes.

Abstract: A protein is usually classified into one of the following five struc- tural classes: a!, j3, a! +j3, a!/j3, and ( (irregular). The structural class of aprotein is correlated with its amino acid composition. However, given the amino acid composition of aprotein, how may one predict its structural class? Various efforts have been made in addressing this problem. This review addresses the progress in this field, with the focus on the state of the art, which is featured by a novel prediction algorithm and a recently developed database. The novel algorithm is characterized by a covariance matrix that takes into account the coupling effect among different amino acid components of a protein. The new database was established based on the requirement that the classes should have (1) as many nonhomologous structures as possible, (2) good quality structure, and (3) typical or distinguishable features for each of the structural classes concerned. The very high success rate for both the training-set proteins and the testing-set proteins, which has been further validated by a simulated analysis and a jackknife analysis, indicates that it is possible to predict the structural class of a protein according to its amino acid composition if an ideal and complete database can be established. It also suggests that the overall fold of a protein is basically determined by its amino acid composition.

Enzymatic degradation of glycosaminoglycans.

Abstract: Glycosaminoglycans (GAGs) play an intricate role in the extracellular matrix (ECM), not only as soluble components and polyelectrolytes, but also by specific interactions with growth factors and other transient components of the ECM. Modifications of GAG chains, such as isomerization, sulfation, and acetylation, generate the chemical specificity of GAGs. GAGs can be depolymerized enzymatically either by eliminative cleavage with lyases (EC 4.2.2.-) or by hydrolytic cleavage with hydrolases (EC 3.2.1.-). Often, these enzymes are specific for residues in the polysaccharide chain with certain modifications. As such, the enzymes can serve as tools for studying the physiological effect of residue modifications and as models at the molecular level of protein-GAG recognition. This review examines the structure of the substrates, the properties of enzymatic degradation, and the enzyme substrate-interactions at a molecular level. The primary structure of several GAGs is organized macroscopically by segregation into alternating blocks of specific sulfation patterns and microscopically by formation of oligosaccharide sequences with specific binding functions. Among GAGs, considerable dermatan sulfate, heparin and heparan sulfate show conformational flexibility in solution. They elicit sequence-specific interactions with enzymes that degrade them, as well as with other proteins, however, the effect of conformational flexibility on protein-GAG interactions is not clear. Recent findings have established empirical rules of substrate specificity and elucidated molecular mechanisms of enzyme-substrate interactions for enzymes that degrade GAGs. Here we propose that local formation of polysaccharide secondary structure is determined by the immediate sequence environment within the GAG polymer, and that this secondary structure, in turn, governs the binding and catalytic interactions between proteins and GAGs.

The Multiple Functions of Hemoglobin

Abstract: The aim of this review is to focus and discuss several parallel biological functions of hemoglobin besides its basic function of oxygen transport. In light of the information present in the literature the following possible physiological roles of hemoglobin are discussed: (1) hemoglobin as molecular heat transducer through its oxygenation-deoxygenation cycle, (2) hemoglobin as modulator of erythrocyte metabolism, (3) hemoglobin oxidation as an onset of erythrocyte senescence, (4) hemoglobin and its implication in genetic resistance to malaria, (5) enzymatic activities of hemoglobin and interactions with drugs, and (6) hemoglobin as source of physiological active catabolites.

Nucleo-Mitochondrial Interactions in Mitochondrial Gene Expression

Abstract: All proteins encoded by mitochondrial DNA (mtDNA) are dependent on proteins encoded by nuclear genes for their synthesis and function. Recent developments in the identification of these genes and the elucidation of the roles their products play at various stages of mitochondrial gene expression are covered in this review, which focuses mainly on work with the yeast Saccharomyces cerevisiae. The high degree of evolutionary conservation of many cellular processes between this yeast and higher eukaryotes, the ease with which mitochondrial biogenesis can be manipulated both genetically and physiologically, and the fact that it will be the first organism for which a complete genomic sequence will be available within the next 2 to 3 years makes it the organism of choice for drawing up an inventory of all nuclear genes involved in mitochondrial biogenesis and for the identification of their counterparts in other organisms.

Protein structure prediction: recognition of primary, secondary, and tertiary structural features from amino acid sequence.

Abstract: This review attempts a critical stock-taking of the current state of the science aimed at predicting structural features of proteins from their amino acid sequences. At the primary structure level, methods are considered for detection of remotely related sequences and for recognizing amino acid patterns to predict posttranslational modifications and binding sites. The techniques involving secondary structural features include prediction of secondary structure, membrane-spanning regions, and secondary structural class. At the tertiary structural level, methods for threading a sequence into a mainchain fold, homology modeling and assigning sequences to protein families with similar folds are discussed. A literature analysis suggests that, to date, threading techniques are not able to show their superiority over sequence pattern recognition methods. Recent progress in the state of ab initio structure calculation is reviewed in detail. The analysis shows that many structural features can be predicted from the amino acid sequence much better than just a few years ago and with attendant utility in experimental research. Best prediction can be achieved for new protein sequences that can be assigned to well-studied protein families. For single sequences without homologues, the folding problem has not yet been solved.

Intestinal Brush Border Glycohydrolases: Structure, Function, and Development

Abstract: The hydrolytic enzymes of the intestinal brush border membrane are essential for the degradation of nutrients to absorbable units. Particularly, the brush border glycohydrolases are responsible for the degradation of di- and oligosaccharides into monosaccharides, and are thus crucial for the energy-intake of humans and other mammals. This review will critically discuss all that is known in the literature about intestinal brush border glycohydrolases. First, we will assess the importance of these enzymes in degradation of dietary carbohydrates. Then, we will closely examine the relevant features of the intestinal epithelium which harbors these glycohydrolases. Each of the glycohydrolytic brush border enzymes will be reviewed with respect to structure, biosynthesis, substrate specificity, hydrolytic mechanism, gene regulation and developmental expression. Finally, intestinal disorders will be discussed that affect the expression of the brush border glycohydrolases. The clinical consequences of these enzyme deficiency disorders will be discussed. Concomitantly, these disorders may provide us with important details regarding the functions and gene expression of these enzymes under specific (pathogenic) circumstances.

Structures of Protein Complexes by Multidimensional Heteronuclear Magnetic Resonance Spectroscopy

Abstract: With the advent of multidimensional heteronuclear-edited and -filtered NMR experiments, the field of three-dimensional structure determination by NMR has again increased in scope, making it possible to move the technology beyond the approximately 10 kDa limit inherent to conventional two-dimensional NMR to systems up to potentially 35 to 40 kDa. This article outlines the basic strategies for solving three-dimensional structures of larger systems, in particular, protein complexes and multimeric proteins using three- and four-dimensional NMR spectroscopy, summarizes the key experiments, and illustrates the power of these methods using several examples of protein-DNA, protein-peptide complexes, and oligomeric proteins from the authors' laboratories.

New Insight into the Biochemical Pathology of Liver in Choline Deficiency

Abstract: A diet deficient in choline can cause liver cancer in rats. The previous work since 1932 emphasized the fat-removing ability of choline from the liver. There are other dietary factors, including methionine, which, like choline, can remove fat from the liver. These factors were termed as lipotropes. Since then, choline deficiency and lipotrope deficiency are used synonoumously. Recent work since 1980 has clearly demonstrated that choline deficiency (CD) and lipotrope deficiency (LD) are not the same. Generation of free radicals, DNA alterations, liver cell death, and liver cancer that occur due to CD are not generated by LD. Generation of free radicals due to CD diet and some of the agents that counteract free radical action also prevent CD effects except for lipid accumulation in the liver. Despite the recent observations on the role of phospholipase A, (PLA) as the protector of the membranes, it has been found that by preventing the rise of PLA, in the liver, cell death can be prevented. These ne...