The role of the imidazolyl nitrogen atoms of histidine-12 in ribonuclease S

Batenburg, O.D. van; Voskuyl-Holtkamp, Ingrid; Schattenkerk, Cecile; Hoes, K; Kerling, K. E. T.; Havinga, E.

doi:10.1042/bj1630385

Cited by 21 publications

(3 citation statements)

References 15 publications

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“…of the imidazole moiety of histidine in the active site of many enzymes (Fersht, 1985;Walsh, 1979), histidinyl residues of peptide ligands have also been shown to influence binding to protein receptors. In a series of thorough experiments it was shown that the His residue of the S-peptide (residues 1-20) of ribonuclease A influenced both binding of S-peptide to S-protein (residues 21-124) and the activity of the resulting peptide-protein complex (Dunn et al, 1974;Van Batenburg et al, 1977).…”

Section: Discussionmentioning

confidence: 99%

Histidine2 of the .alpha.-factor of Saccharomyces cerevisiae is not essential for binding to its receptor or for biological activity

Levin¹,

Khare²,

Abel³

et al. 1993

Biochemistry

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Seven His2 analogs of the Saccharomyces cerevisiae [Nle12]alpha-factor, WXWLQLKPGQP(Nle)Y, where X = beta-D-thienylalanine, beta-L-thienylalanine, 1-D-methylhistidine, 1-L-methylhistidine, 3-D-methylhistidine, 3-L-methylhistidine, and beta-3-L-pyridylalanine, were synthesized and purified to homogeneity. Assays were carried out on binding to the alpha-factor receptor and of biological activity determined by either growth arrest or morphological changes in target cells. In the L-isomer, replacement of the imidazole of histidine by thiophene or 3-pyridyl groups or derivatization of either nitrogen of the imidazole ring by methylation resulted in a 2-100-fold decrease in bioactivity. D-Isomers of the beta-thienylalanyl-, 1-methylhistidinyl-, or 3-methylhistidinyl-alpha-factors did not possess measurable bioactivity with the exception of comparatively low activity of the 3-D-methylhistidinyl and 1-D-methylhistidinyl-alpha-factors in the morphogenesis assay. In contrast, both active and inactive analogs demonstrated binding affinities 10-20-fold less than that of [Nle12]alpha-factor. These results indicate that the histidine residue of alpha-factor is not required for binding to the receptor or for biological activity and that bioactivity and binding can be dissociated through the use of pheromone analogs.

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Section: Discussionmentioning

confidence: 99%

Histidine2 of the .alpha.-factor of Saccharomyces cerevisiae is not essential for binding to its receptor or for biological activity

Levin¹,

Khare²,

Abel³

et al. 1993

Biochemistry

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“…A growing interest has recently been focused on the synthesis of unnatural α-amino acids; their use in the fields of peptide and combinatorial chemistry as conformational constraints, molecular scaffolds, and chiral auxiliaries is related to the development of new leads in peptidic and nonpeptidic compounds . The class of nonproteinogenic heterocyclic α-amino acids is of particular interest in this context due to their diverse range of chemical and biomedicinal applications not only as components of peptides and peptide nucleic acids (PNAs) but also as free amino acids (e.g. the antitumor−antibiotic agent l -azatyrosine 4a ).…”

Section: Introductionmentioning

confidence: 99%

Model Studies toward the Synthesis of Dihydropyrimidinyl and Pyridyl α-Amino Acids via Three-Component Biginelli and Hantzsch Cyclocondensations

et al. 2003

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A novel and versatile strategy for the synthesis of heterocyclic alpha-amino acids has been described. The use of components (aldehyde or beta-ketoester) bearing a masked glycinyl moiety in Biginelli and Hantzsch cyclocondensations allowed access to the 4-dihydropyrimidinyl-alpha-glycines, 4-dihydropyrimidinyl-alpha-alanines, 4-pyridyl-alpha-alanines, and 2-pyridyl-alpha-alanines classes. Dihydropyrimidinyl-amino acids were obtained as a mixture of diastereoisomers due to the formation of the stereocenter at C4 of the dihydropyrimidinone ring. Individual stereoisomers were isolated as pure compounds and their structures were assigned with the aid of X-ray crystallography and chiroptical properties. The enantiomeric purity of a representative selection of the above amino acids was greater than 96% as verified by derivatization to the corresponding Mosher's amides and subsequent (1)H and (19)F NMR spectroscopy. Incorporation of the 4-pyridyl-alpha-alanine derivative into a peptide chain is also described.

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“…When combined together in a non-covalent complex, the two peptide segments combine to form an enzyme with 100% activity. This type of peptide or fragment complementation system was the first system in which "mutants" of the wild type enzyme could be tested in an in vitro assay system, as it allowed for a number of amino acids to be substituted for in the wild type enzyme by direct replacement of the amino acid via peptide synthesis (24). A number of other examples of peptide complementation are known in the literature including S. aureus nuclease, soybean trypsin inhibitor, and thioredoxin (25)(26)(27).…”

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confidence: 99%

Semisynthesis and Characterization of Mammalian Thioredoxin Reductase

et al. 2006

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Thioredoxin reductase and thioredoxin constitute the cellular thioredoxin system, which provides reducing equivalents to numerous intracellular target disulfides. Mammalian thioredoxin reductase contains the rare amino acid selenocysteine. Known as the "21st" amino acid, selenocysteine is inserted into proteins by recoding UGA stop codons. Some model eukaryotic organisms lack the ability to insert selenocysteine, and prokaryotes have a recoding apparatus different from that of eukaryotes, thus making heterologous expression of mammalian selenoproteins difficult. Here, we present a semisynthetic method for preparing mammalian thioredoxin reductase. This method produces the first 487 amino acids of mouse thioredoxin reductase-3 as an intein fusion protein in Escherichia coli cells. The missing C-terminal tripeptide containing selenocysteine is then ligated to the thioester-tagged protein by expressed protein ligation. The semisynthetic version of thioredoxin reductase that we produce in this manner has k(cat) values ranging from 1500 to 2220 min(-)(1) toward thioredoxin and has strong peroxidase activity, indicating a functional form of the enzyme. We produced the semisynthetic thioredoxin reductase with a total yield of 24 mg from 6 L of E. coli culture (4 mg/L). This method allows production of a fully functional, semisynthetic selenoenzyme that is amenable to structure-function studies. A second semisynthetic system is also reported that makes use of peptide complementation to produce a partially active enzyme. The results of our peptide complementation studies reveal that a tetrapeptide that cannot ligate to the enzyme (Ac-Gly-Cys-Sec-Gly) can form a noncovalent complex with the truncated enzyme to form a weak complex. This noncovalent peptide-enzyme complex has 350-500-fold lower activity than the semisynthetic enzyme produced by peptide ligation.

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The role of the imidazolyl nitrogen atoms of histidine-12 in ribonuclease S

Cited by 21 publications

References 15 publications

Histidine2 of the .alpha.-factor of Saccharomyces cerevisiae is not essential for binding to its receptor or for biological activity

Histidine2 of the .alpha.-factor of Saccharomyces cerevisiae is not essential for binding to its receptor or for biological activity

Model Studies toward the Synthesis of Dihydropyrimidinyl and Pyridyl α-Amino Acids via Three-Component Biginelli and Hantzsch Cyclocondensations

Semisynthesis and Characterization of Mammalian Thioredoxin Reductase

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