scholarly journals Structural-based engineering expands the substrate scope of a cyclodipeptide synthase

2021 ◽  
Author(s):  
Emmajay Sutherland ◽  
Christopher Harding ◽  
Clarissa Czekster
Keyword(s):  
Crystal Structure ◽  
Amino Acids ◽  
Biological Activities ◽  
Substrate Selectivity ◽  
Cyclic Dipeptides ◽  
Successive Generations ◽  
The Way

Cyclodipeptide synthases (CDPSs) are a growing family of enzymes capable of producing a large variety of cyclodipetide products using aminoacylated tRNA. Histidine-containing cyclic dipeptides have important biological activities as anticancer and neuroprotective molecules. Out of the 120 experimentally validated CDPS members, only two are known to accept histidine as a substrate. Here, we studied the activities of both Para-CDPS from Parabacteroides sp. 20_3 and Parcu-CDPS from Parcubacteria bacterium RAAC4_OD1_1 which synthesise cyclo(His-Phe) and cyclo(His-Pro) respectively. Both enzymes accepted canonical and non-canonical amino acids as substrates to generate a library of novel molecules. In order to understand the substrate selectivity of these CDPSs, the crystal structure of Parcu-CDPS was solved (alongside a number of mutants) and the role of residues important for catalysis and histidine recognition were probed using mutagenesis. Three successive generations of mutants containing both single and double residue substitutions were generated leading to a change in substrate selectivity from histidine to phenylalanine and leucine. The research detailed herein is the first instance of successful engineering of a CDPS to yield different products, paving the way to direct the promiscuity of these enzymes to produce molecules of our choosing.

Lamotriginium crotonate and lamotriginium salicylate ethanol monosolvate: the role of solvent molecules in the packing organization

2017 ◽  
Vol 73 (7) ◽  
pp. 563-568
Author(s):  
Eleonora Freire ◽  
Gustavo A. Echeverría ◽  
Ricardo Baggio
Keyword(s):  
Crystal Structure ◽  
Building Blocks ◽  
Solvent Molecules ◽  
Role Of Solvent ◽  
The Way ◽  
Hydrogen Bonded

Two lamotriginium salts, namely lamotriginium crotonate [systematic name: 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazin-2-ium but-2-enoate, C9H8Cl2N5 +·C4H5O2 −, (III)] and lamotriginium salicylate [systematic name: 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazin-2-ium 2-hydroxybenzoate ethanol monosolvate, C9H8Cl2N5 +·C7H5O3 −·C2H5OH, (IV)] present extremely similar centrosymmetric hydrogen-bonded A...L...L...A packing building blocks (L is lamotriginium and A is the anion). The fact that salicylate salt (IV) is (ethanol) solvated, while crotonate salt (III) is not, has a profound effect on the way these elemental units aggregate to generate the final crystal structure. Possible reasons for this behaviour are analyzed and the hypothesis raised checked against similar structures in the literature.

scholarly journals Caseins as Regulators of Hematopoiesis

2020 ◽  
Author(s):  
Edgar Ledesma-Martinez ◽  
Vanihamin Domínguez-Meléndez ◽  
Itzen Aguiñiga-Sánchez ◽  
Edelmiro Santiago-Osorio
Keyword(s):  
Amino Acids ◽  
Biological Activities ◽  
Physiological Role ◽  
Antimicrobial Activities ◽  
Strong Immune Response ◽  
Physiological Importance ◽  
Immunosuppressed Patients ◽  
Main Protein ◽  
Over Time

The main physiological role of casein, the main protein component in the milk, is to be a source of amino acids that are required for the growth of the neonate; therefore, casein is considered a highly nutritious protein. Over time, it has been revealed that casein is a protein whose physiological importance reaches levels far superior to the food field, having a wide array of biological activities including antimicrobial activities, facilitating absorption of nutrients, as well as acting as a growth factor and an immune stimulant. Here we analyze how caseins can exert numerous hematopoietic and immunomodulatory actions, their role in granulopoiesis, monocytopoiesis, and lymphopoiesis from the early stages of postnatal development seemingly throughout life, and we wonder if casein could be useful to fight pathogens resistant to antibiotics, inducing a strong immune response in immunosuppressed patients, or even be a prophylactic strategy to prevent infections.

MANUSCRIPT EVIDENCE FOR ALPHABET-SWITCHING IN THE WORKS OF CICERO: COMMON NOUNS AND ADJECTIVES

2018 ◽  
Vol 68 (2) ◽  
pp. 498-516
Author(s):  
Neil O'Sullivan
Keyword(s):  
Recent Work ◽  
Code Switching ◽  
Consistent Pattern ◽  
Current Interest ◽  
Reliable Transmission ◽  
Accurate Record ◽  
The Way

Of the hundreds of Greek common nouns and adjectives preserved in our MSS of Cicero, about three dozen are found written in the Latin alphabet as well as in the Greek. So we find, alongside συμπάθεια, also sympathia, and ἱστορικός as well as historicus. This sort of variation has been termed alphabet-switching; it has received little attention in connection with Cicero, even though it is relevant to subjects of current interest such as his bilingualism and the role of code-switching and loanwords in his works. Rather than addressing these issues directly, this discussion sets out information about the way in which the words are written in our surviving MSS of Cicero and takes further some recent work on the presentation of Greek words in Latin texts. It argues that, for the most part, coherent patterns and explanations can be found in the alphabetic choices exhibited by them, or at least by the earliest of them when there is conflict in the paradosis, and that this coherence is evidence for a generally reliable transmission of Cicero's original choices. While a lack of coherence might indicate unreliable transmission, or even an indifference on Cicero's part, a consistent pattern can only really be explained as an accurate record of coherent alphabet choice made by Cicero when writing Greek words.

Role of amino acids and micronutrients on biosynthesis of spiramycins

1981 ◽  
Vol 31 (1) ◽  
pp. 189-193 ◽  
Author(s):  
Mohamed A. Ashy ◽  
Abd El-Galil ◽  
M. Khalil ◽  
Abou-Zeid A. Abou-Zeid
Keyword(s):  
Amino Acids

The adaptation of design thinking in auditing

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Linda MEIJER-WASSENAAR ◽  
Diny VAN EST
Keyword(s):  
The Netherlands ◽  
Design Thinking ◽  
Public Organizations ◽  
Design Framework ◽  
The Right ◽  
The Way

How can a supreme audit institution (SAI) use design thinking in auditing? SAIs audit the way taxpayers’ money is collected and spent. Adding design thinking to their activities is not to be taken lightly. SAIs independently check whether public organizations have done the right things in the right way, but the organizations might not be willing to act upon a SAI’s recommendations. Can you imagine the role of design in audits? In this paper we share our experiences of some design approaches in the work of one SAI: the Netherlands Court of Audit (NCA). Design thinking needs to be adapted (Dorst, 2015a) before it can be used by SAIs such as the NCA in order to reflect their independent, autonomous status. To dive deeper into design thinking, Buchanan’s design framework (2015) and different ways of reasoning (Dorst, 2015b) are used to explore how design thinking can be adapted for audits.

Bad Dreams and Secret Artists: Translating Freud into Literature

2002 ◽  
Vol 4 (2) ◽  
pp. 127-139 ◽  
Author(s):  
Ian Patterson
Keyword(s):  
Sigmund Freud ◽  
Ordinary Language ◽  
Close Reading ◽  
Careful Attention ◽  
Popular Approach ◽  
English Reader ◽  
Creative Writer ◽  
The Many ◽  
The Way

This article addresses the increasingly popular approach to Freud and his work which sees him primarily as a literary writer rather than a psychologist, and takes this as the context for an examination of Joyce Crick's recent translation of The Interpretation of Dreams. It claims that translation lies at the heart of psychoanalysis, and that the many interlocking and overlapping implications of the word need to be granted a greater degree of complexity. Those who argue that Freud is really a creative writer are themselves doing a work of translation, and one which fails to pay sufficiently careful attention to the role of translation in writing itself (including the notion of repression itself as a failure to translate). Lesley Chamberlain's The Secret Artist: A Close Reading of Sigmund Freud is taken as an example of the way Freud gets translated into a novelist or an artist, and her claims for his ‘bizarre poems' are criticized. The rest of the article looks closely at Crick's new translation and its claim to be restoring Freud the stylist, an ordinary language Freud, to the English reader. The experience of reading Crick's translation is compared with that of reading Strachey's, rather to the latter's advantage.

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