ADMET polymers: synthesis, structure elucidation, and function

AbstractGlycosyltransferases (GTs) play fundamental roles in nearly all cellular processes through the biosynthesis of complex carbohydrates and glycosylation of diverse protein and small molecule substrates. The extensive structural and functional diversification of GTs presents a major challenge in mapping the relationships connecting sequence, structure, fold and function using traditional bioinformatics approaches. Here, we present a convolutional neural network with attention (CNN-attention) based deep learning model that leverages simple secondary structure representations generated from primary sequences to provide GT fold prediction with high accuracy. The model learns distinguishing secondary structure features free of primary sequence alignment constraints and is highly interpretable. It delineates sequence and structural features characteristic of individual fold types, while classifying them into distinct clusters that group evolutionarily divergent families based on shared secondary structural features. We further extend our model to classify GT families of unknown folds and variants of known folds. By identifying families that are likely to adopt novel folds such as GT91, GT96 and GT97, our studies expand the GT fold landscape and prioritize targets for future structural studies.

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Bifunctional Chloroplastic DJ-1B from Arabidopsis thaliana is an Oxidation-Robust Holdase and a Glyoxalase Sensitive to H2O2

Antioxidants ◽

10.3390/antiox8010008 ◽

2019 ◽

Vol 8 (1) ◽

pp. 8 ◽

Cited By ~ 4

Author(s):

Aleksandra Lewandowska ◽

Trung Nghia Vo ◽

Thuy-Dung Ho Nguyen ◽

Khadija Wahni ◽

Didier Vertommen ◽

...

Keyword(s):

Oxidative Stress ◽

Arabidopsis Thaliana ◽

Secondary Structure ◽

Structure And Function ◽

Transcript Levels ◽

Chaperone Function ◽

Multifunctional Enzymes ◽

And Function ◽

Discrete Functions

Members of the DJ-1 protein family are multifunctional enzymes whose loss increases the susceptibility of the cell to oxidative stress. However, little is known about the function of the plant DJ-1 homologs. Therefore, we analyzed the effect of oxidation on the structure and function of chloroplastic AtDJ-1B and studied the phenotype of T-DNA lines lacking the protein. In vitro oxidation of AtDJ-1B with H2O2 lowers its glyoxalase activity, but has no effect on its holdase chaperone function. Remarkably, upon oxidation, the thermostability of AtDJ-1B increases with no significant alteration of the overall secondary structure. Moreover, we found that AtDJ-1B transcript levels are invariable, and loss of AtDJ-1B does not affect plant viability, growth and stress response. All in all, two discrete functions of AtDJ-1B respond differently to H2O2, and AtDJ-1B is not essential for plant development under stress.

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Secondary structure of U6 small nuclear RNA: implications for spliceosome assembly

Biochemical Society Transactions ◽

10.1042/bst0381099 ◽

2010 ◽

Vol 38 (4) ◽

pp. 1099-1104 ◽

Cited By ~ 9

Author(s):

Elizabeth A. Dunn ◽

Stephen D. Rader

Keyword(s):

Secondary Structure ◽

Small Nuclear Rna ◽

Stem Loop ◽

New Model ◽

Rna Molecules ◽

U6 Snrna ◽

Small Nuclear Ribonucleoprotein ◽

Nuclear Rna ◽

High Level ◽

And Function

U6 snRNA (small nuclear RNA), one of five RNA molecules that are required for the essential process of pre-mRNA splicing, is notable for its high level of sequence conservation and the important role it is thought to play in the splicing reaction. Nevertheless, the secondary structure of U6 in the free snRNP (small nuclear ribonucleoprotein) form has remained elusive, with predictions changing substantially over the years. In the present review we discuss the evidence for existing models and critically evaluate a fundamental assumption of these models, namely whether the important 3′ ISL (3′ internal stem–loop) is present in the free U6 particle, as well as in the active splicing complex. We compare existing models of free U6 with a newly proposed model lacking the 3′ ISL and evaluate the implications of the new model for the structure and function of U6's base-pairing partner U4 snRNA. Intriguingly, the new model predicts a role for U4 that was unanticipated previously, namely as an activator of U6 for assembly into the splicing machinery.

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Effects of osmolytes and macromolecular crowders on stable GAAA tetraloops and their preference for a CG closing base pair

PeerJ ◽

10.7717/peerj.4236 ◽

2018 ◽

Vol 6 ◽

pp. e4236

Author(s):

Kaethe N. Leonard ◽

Joshua M. Blose

Keyword(s):

Secondary Structure ◽

Base Pair ◽

Structural Changes ◽

Tertiary Structure ◽

Vis Spectroscopy ◽

Rna Tertiary Structure ◽

The Stability ◽

And Function ◽

Peg 8000

Osmolytes and macromolecular crowders have the potential to influence the stability of secondary structure motifs and alter preferences for conserved nucleic acid sequences in vivo. To further understand the cellular function of RNA we observed the effects of a model osmolyte, polyethylene glycol (PEG) 200, and a model macromolecular crowding agent, PEG 8000, on the GAAA tetraloop motif. GAAA tetraloops are conserved, stable tetraloops, and are critical participants in RNA tertiary structure. They also have a thermodynamic preference for a CG closing base pair. The thermal denaturation of model hairpins containing GAAA loops was monitored using UV-Vis spectroscopy in the presence and absence of PEG 200 or PEG 8000. Both of the cosolutes tested influenced the thermodynamic preference for a CG base pair by destabilizing the loop with a CG closing base pair relative to the loop with a GC closing base pair. This result also extended to a related DNA triloop, which provides further evidence that the interactions between the loop and closing base pair are identical for the d(GCA) triloop and the GAAA tetraloop. Our results suggest that in the presence of model PEG molecules, loops with a GC closing base pair may retain some preferential interactions with the cosolutes that are lost in the presence of the CG closing base pair. These results reveal that relatively small structural changes could influence how neutral cosolutes tune the stability and function of secondary structure motifs in vivo.

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Dissymmetric Chiral Poly(diphenylacetylene)s: Secondary Structure Elucidation and Dynamic Luminescence

Angewandte Chemie International Edition ◽

10.1002/anie.202115070 ◽

2022 ◽

Author(s):

Felix Freire ◽

Juan José Tarrío ◽

Rafael Rodríguez ◽

Berta Fernández ◽

Emilio Quiñoá

Keyword(s):

Secondary Structure ◽

Structure Elucidation

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Sequence Diversity and Functional Conservation of the Origin of Replication in Lactococcal Prolate Phages

Applied and Environmental Microbiology ◽

10.1128/aem.69.9.5104-5114.2003 ◽

2003 ◽

Vol 69 (9) ◽

pp. 5104-5114 ◽

Cited By ~ 7

Author(s):

Jasna Rakonjac ◽

Lawrence J. H. Ward ◽

Anja H. Schiemann ◽

Paul P. Gardner ◽

Mark W. Lubbers ◽

...

Keyword(s):

Dna Replication ◽

Secondary Structure ◽

Sequence Homology ◽

Plasmid Replication ◽

Origin Of Replication ◽

Functional Conservation ◽

Origins Of Replication ◽

Flanking Sequences ◽

And Function ◽

Phage Proteins

ABSTRACT Prolate or c2-like phages are a large homologous group of viruses that infect the bacterium Lactococcus lactis. In a collection of 122 prolate phages, three distinct, non-cross-hybridizing groups of origins of DNA replication were found. The nonconserved sequence was confined to the template for an untranslated transcript, PE1-T, 300 to 400 nucleotides in length, while the flanking sequences were conserved. All three origin types, despite the low sequence homology, have the same functional characteristics: they express abundant PE1-T transcripts and can function as origins of plasmid replication in the absence of phage proteins. Using chimeric constructs, we showed that hybrids of two nonhomologous origin sequences failed to function as replication origins, suggesting that preservation of a particular secondary structure of the PE1-T transcript is required for replication. This is the first systematic survey of the sequence and function of origins of replication in a group of lactococcal phages.

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