Selective interactions between mimivirus uracil-DNA glycosylase and inhibitory proteins determined by a single amino acid

Pathak, Deepak; Kwon, Eunju; Kim, Dong Young

doi:10.1016/j.jsb.2020.107552

Cited by 3 publications

(2 citation statements)

References 41 publications

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“…Table 1 ) is the most effective (with an IC 50 value of 7.6 pM) [ 43 , 44 , 45 ]. However, the UGI protein does not show a universal inhibitions against UNG enzymes from any sources, e.g., poxvirus, Vaccinia virus and Mimivirus UNGs are not inhibited by UGI [ 46 ]. Still, E. coli UNG irreversibly inhibited by UGI [ 5 ].…”

Section: Ung Inhibitors and Their Potential Biotechnological Applicationsmentioning

confidence: 99%

Viruses with U-DNA: New Avenues for Biotechnology

Nagy

Skurnik

Vértessy

2021

Viruses

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Deoxyuridine in DNA has recently been in the focus of research due to its intriguing roles in several physiological and pathophysiological situations. Although not an orthodox DNA base, uracil may appear in DNA via either cytosine deamination or thymine-replacing incorporations. Since these alterations may induce mutation or may perturb DNA–protein interactions, free living organisms from bacteria to human contain several pathways to counteract uracilation. These efficient and highly specific repair routes uracil-directed excision repair initiated by representative of uracil-DNA glycosylase families. Interestingly, some bacteriophages exist with thymine-lacking uracil-DNA genome. A detailed understanding of the strategy by which such phages can replicate in bacteria where an efficient repair pathway functions for uracil-excision from DNA is expected to reveal novel inhibitors that can also be used for biotechnological applications. Here, we also review the several potential biotechnological applications already implemented based on inhibitors of uracil-excision repair, such as Crispr-base-editing and detection of nascent uracil distribution pattern in complex genomes.

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Section: Ung Inhibitors and Their Potential Biotechnological Applicationsmentioning

confidence: 99%

Viruses with U-DNA: New Avenues for Biotechnology

Nagy

Skurnik

Vértessy

2021

Viruses

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“…To test if artificially generated structural homologs obtained from Sibs-Seq are useful for structural inference, we first selected a mixed helix/sheet protein: the uracil glycosylase inhibitor (a 83-residue protein of mixed helices and sheets, PDB ID: 6LYD) (38). To locate the best selection pressure for structure prediction, we performed experiments at 9 conditions with TMP concentrations ranging from 25 μg/ml, 100 μg/ml, to 400 μg/ml and incubation time ranging from 1 × 12 h, 2 × 12h, to 3 × 12 h. All variants selected from 9 conditions were sequenced.…”

Section: Initial Test Of Sibs-seq Using the Uracil Glycosylase Inhibitormentioning

confidence: 99%

Effective High-Accuracy Prediction of Protein Structures from Easily Obtainable Artificial Homologous Sequences by Structure-Stability-Based Selection

Tang,

Zhang,

Zhan

et al. 2023

Preprint

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High-resolution protein structure determination by experimental techniques is notoriously costly and labor intensive. This problem is mostly solved with arrival of deep-learning-based computational prediction by AlphaFold2 but only for those proteins with enough naturally occurring homologous sequences. Here, we attempt to close the remaining gap by employing artificially generated, structure-stability-selected homologous sequences as an input for AlphaFold2. We showed that only one round of selection of deeply mutated sequences of a few mutations is sufficient to bring the accuracy of predicted structures to better than 2 Å RMSD from their respective native structures for four of the five proteins experimented. The performance for three out of five proteins is even better than AlphaFold2 with naturally occurring sequences. The only protein with predicted structure of >2 Å (at 2.92 Å) RMSD is due to a fully exposed (i.e., likely flexible) β-hairpin. The result supports a future of determining protein structures at low cost and fast turnaround by integrating simple molecular biology experiments (deep mutational scanning andin vivoorin vitroselection) with high-throughput sequencing. The technique proposed here can be further extended to predict structures of protein complexes as well as proteins with posttranslational modifications.

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