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General Pharmacology 1977
Review
Topics: Alanine; Animals; Central Nervous System; Neurotransmitter Agents
PubMed: 23341
DOI: 10.1016/0306-3623(77)90046-5 -
Biological Chemistry Aug 2013The prospective increase in life expectancy will be accompanied by a rise in the number of elderly people who suffer from ill health caused by old age. Many diseases... (Review)
Review
The prospective increase in life expectancy will be accompanied by a rise in the number of elderly people who suffer from ill health caused by old age. Many diseases caused by aging are protein misfolding diseases. The molecular mechanisms underlying these disorders receive constant scientific interest. In addition to old age, mutations also cause congenital protein misfolding disorders. Chorea Huntington, one of the most well-known examples, is caused by triplet extensions that can lead to more than 100 glutamines in the N-terminal region of huntingtin, accompanied by huntingtin aggregation. So far, nine disease-associated triplet extensions have also been described for alanine codons. The extensions lead primarily to skeletal malformations. Eight of these proteins represent transcription factors, while the nuclear poly-adenylate binding protein 1, PABPN1, is an RNA binding protein. Additional alanines in PABPN1 lead to the disease oculopharyngeal muscular dystrophy (OPMD). The alanine extension affects the N-terminal domain of the protein, which has been shown to lack tertiary contacts. Biochemical analyses of the N-terminal domain revealed an alanine-dependent fibril formation. However, fibril formation of full-length protein did not recapitulate the findings of the N-terminal domain. Fibril formation of intact PABPN1 was independent of the alanine segment, and the fibrils displayed biochemical properties that were completely different from those of the N-terminal domain. Although intranuclear inclusions have been shown to represent the histochemical hallmark of OPMD, their role in pathogenesis is currently unclear. Several cell culture and animal models have been generated to study the molecular processes involved in OPMD. These studies revealed a number of promising future therapeutic strategies that could one day improve the quality of life for the patients.
Topics: Alanine; Amyloid; Animals; Humans; Muscular Dystrophy, Oculopharyngeal; Poly(A)-Binding Protein I; Protein Folding; Proteins
PubMed: 23612654
DOI: 10.1515/hsz-2013-0112 -
Amino Acids Aug 2021Searching for new drugs is still a challenge for science, mainly because of civilization development and globalization which promote the rapid spread of diseases, which...
Searching for new drugs is still a challenge for science, mainly because of civilization development and globalization which promote the rapid spread of diseases, which is particularly dangerous in the case of infectious ones. Moreover, readily available already known antibiotics are often overused or misused, possibly contributing to the increase in the number of multidrug-resistant microorganisms. A consequence of this is the need for new structures of potential drugs. One of them is a benzoxazole moiety, a basic skeleton of a group of fluorescent heterocyclic compounds already widely used in chemistry, industry, and medicine, which is also present in naturally occurring biologically active compounds. Moreover, synthetic benzoxazoles are also biologically active. Considering all of that, a large group of non-proteinogenic amino acids based on 3-(2-benzoxazol-5-yl)alanine skeleton was studied in search for new antimicrobial and anticancer agents. Screening tests revealed that antibacterial potential of 41 compounds studied is not very high; however, they are selective acting only against Gram-positive bacteria (B. subtilis). Moreover, almost half of the studied compounds have antifungal properties, also against pathogens (C. albicans). Most of studied compounds are toxic to both normal and cancer cells. However, in a few cases, toxicity to normal cells is much lower than for cancer cells indicating these compounds as future anticancer agents. The research carried out on such a large group of compounds allowed to establish a structure-activity relationship which enables to select candidates for further modifications, necessary to improve their biological activity and obtain a new lead structure with potential for therapeutic use.
Topics: Alanine; Animals; Candida albicans; Cell Line, Tumor; Drug Screening Assays, Antitumor; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Rats; Structure-Activity Relationship
PubMed: 34240252
DOI: 10.1007/s00726-021-03030-7 -
Biological & Pharmaceutical Bulletin Sep 2005Aquatic crustaceans and some bivalve mollusks contain a large amount of free D-alanine (up to 100 mumol/g wet wt.) in their tissues. Under high salinity stress,... (Review)
Review
Aquatic crustaceans and some bivalve mollusks contain a large amount of free D-alanine (up to 100 mumol/g wet wt.) in their tissues. Under high salinity stress, crustaceans and bivalve mollusks largely accumulate D- and L-alanine irrespective of species examined, together with L-glutamine, L-proline, and glycine of which increases are species dependent. These data indicate that D-alanine is one of the major compatible osmolytes responsible for the intracellular isosmotic regulation in the tissues of crustaceans and bivalves. Alanine racemase has been proven to catalyze the interconversion of D- and L-alanine in these invertebrates. The enzyme has been isolated to homogeneity from the muscle of black tiger prawn Penaeus monodon and its cDNA has been cloned from the muscle and hepatopancreas of kuruma prawn Penaeus japonicus for the first time in eukaryotes other than yeast. Several fish species fed on crustaceans and mollusks contain D-amino acid and D-aspartate oxidases that catalyze the decomposition of D-amino acids. A cDNA of D-amino acid oxidase has been cloned from the hepatopancreas of omnivorous common carp Cyprinus carpio. During oral administration of free D-alanine to carp, the activity and mRNA of D-amino acid oxidase increased rapidly in hepatopancreas and the increases were highest in intestine followed by hepatopancreas and kidney. These data suggest that D-amino acid oxidase is inducible in carp and an important enzyme responsible for the efficient utilization of carbon skeleton of D-alanine in their feeds.
Topics: Alanine; Animals; Fishes; Hypoxia; Invertebrates; Osmolar Concentration
PubMed: 16141518
DOI: 10.1248/bpb.28.1571 -
Pharmacology & Therapeutics 1981
Review
Topics: Alanine; Bacteria; Biological Transport, Active; Cell Wall; Depression, Chemical; Drug Resistance, Microbial
PubMed: 7034001
DOI: 10.1016/0163-7258(81)90030-9 -
Biochemistry and Cell Biology =... Apr 2010Antifreeze proteins (AFPs) protect cold-blooded organisms from the damage caused by freezing through their ability to inhibit ice growth. The type I AFP family, found in... (Review)
Review
Antifreeze proteins (AFPs) protect cold-blooded organisms from the damage caused by freezing through their ability to inhibit ice growth. The type I AFP family, found in several fish species, contains proteins that have a high alanine content (>60% of the sequence) and structures that are almost all alpha-helical. We examine the structure of the type I AFP isoforms HPLC6 from winter flounder, shorthorn sculpin 3, and the winter flounder hyperactive type I AFP. The HPLC6 isoform structure consists of a single alpha-helix that is 37 residues long, whereas the shorthorn sculpin 3 isoform consists of two helical regions separated by a kink. The high-resolution structure of the hyperactive type I AFP has yet to be determined, but circular dichroism data and analytical ultracentrifugation suggest that the 195 residue protein is a side-by-side dimer of two alpha-helices. The alanine-rich ice-binding faces of HPLC6 and hyperactive type I AFP are discussed, and we propose that the ice-binding face of the shorthorn sculpin 3 AFP contains Ala14, Ala19, and Ala25. We also propose that the denaturation of hyperactive type I AFP at room temperature is explained by the stabilization of the dimerization interface through hydrogen bonds.
Topics: Alanine; Antifreeze Proteins, Type I; Binding Sites; Ice; Protein Conformation
PubMed: 20453925
DOI: 10.1139/o09-183 -
Physical Chemistry Chemical Physics :... Dec 2022The relationship between protein sequence and its thermodynamic stability is a critical aspect of computational protein design. In this work, we present a new...
The relationship between protein sequence and its thermodynamic stability is a critical aspect of computational protein design. In this work, we present a new theoretical method to calculate the free energy change (ΔΔ) resulting from a single-point amino acid mutation to alanine in a protein sequence. The method is derived based on physical interactions and is very efficient in estimating the free energy changes caused by a series of alanine mutations from just a single molecular dynamics (MD) trajectory. Numerical calculations are carried out on a total of 547 alanine mutations in 19 diverse proteins whose experimental results are available. The comparison between the experimental ΔΔ and the calculated values shows a generally good correlation with a correlation coefficient of 0.67. Both the advantages and limitations of this method are discussed. This method provides an efficient and valuable tool for protein design and engineering.
Topics: Alanine; Proteins; Thermodynamics; Mutation; Amino Acid Sequence
PubMed: 36449314
DOI: 10.1039/d2cp04236c -
Voprosy Meditsinskoi Khimii 1981
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The Journal of Biological Chemistry Sep 1950
Topics: Alanine; beta-Alanine
PubMed: 14778839
DOI: No ID Found -
Food Chemistry Apr 2022Metal ions are known to influence the course of the Maillard reaction through formation of various complexes such as bis(amino acids), these complexes are known to...
Metal ions are known to influence the course of the Maillard reaction through formation of various complexes such as bis(amino acids), these complexes are known to undergo more facile reaction with sugars. Due to this enhanced reactivity, the possible formation of di-glycated amino acids in glucose/alanine model systems with and without FeCl was investigated using isotope labelling technique in conjunction with ESI/qTOF/MS/MS. Forty-eight derivatives of bis[N,N'-di-glycated alanine] iron(II) complexes were tentatively identified. These complexes incorporated one iron atom, two [C-3] atoms from alanine and up-to twenty-four carbon atoms from glucose [C-U], were incorporated as triose (C3), tetrose (C4), pentose (C5) or hexose (C6) moieties. Furthermore, the dissociation of the above complexes released variously substituted N,N-di-glycated alanine derivatives incorporating one alanine [C-3] atom and up to twelve carbon atoms from glucose [C-U]. The MS/MS analysis of diglycated alanines indicated that they follow similar fragmentation pathways as Amadori product of alanine.
Topics: Alanine; Ferrous Compounds; Glucose; Iron; Tandem Mass Spectrometry
PubMed: 34920402
DOI: 10.1016/j.foodchem.2021.131815