Multi-substrate selectivity based on key loops and non-homologous domains: new insight into ALKBH family

Xu, Baofang; Liu, Dongyang; Wang, Zerong; Tian, Ruixia; Zuo, Yongchun

doi:10.1007/s00018-020-03594-9

Cited by 54 publications

(55 citation statements)

References 160 publications

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“…The functional domain of 2OG oxygenases contains Fe 2+binding sites and α-ketoglutarate-binding sites, and their amino acid composition is almost completely conserved. The Fe 2+ -binding motif (HXD-H) and α-KG-binding motif (N-Y-R-R) of the ALKBH family are entirely conserved in the homologs (Bjornstad et al, 2011;Fedeles et al, 2015;Alemu et al, 2016;Xu et al, 2021), and other 2OG oxygenases have similar structures (Bleijlevens et al, 2008;Islam et al, 2018; . They all combine Fe 2+ and α-ketoglutarate through conserved polar amino acid regions, which may be the reason why polarity is an essential feature of 2OG oxygenase identification.…”

Section: Predictive Performance Of Different Reducing Amino Acid Clustermentioning

confidence: 99%

Identification of Disease-Related 2-Oxoglutarate/Fe (II)-Dependent Oxygenase Based on Reduced Amino Acid Cluster Strategy

Zhou

Wang

et al. 2021

Front. Cell Dev. Biol.

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The 2-oxoglutarate/Fe (II)-dependent (2OG) oxygenase superfamily is mainly responsible for protein modification, nucleic acid repair and/or modification, and fatty acid metabolism and plays important roles in cancer, cardiovascular disease, and other diseases. They are likely to become new targets for the treatment of cancer and other diseases, so the accurate identification of 2OG oxygenases is of great significance. Many computational methods have been proposed to predict functional proteins to compensate for the time-consuming and expensive experimental identification. However, machine learning has not been applied to the study of 2OG oxygenases. In this study, we developed OGFE_RAAC, a prediction model to identify whether a protein is a 2OG oxygenase. To improve the performance of OGFE_RAAC, 673 amino acid reduction alphabets were used to determine the optimal feature representation scheme by recoding the protein sequence. The 10-fold cross-validation test showed that the accuracy of the model in identifying 2OG oxygenases is 91.04%. Besides, the independent dataset results also proved that the model has excellent generalization and robustness. It is expected to become an effective tool for the identification of 2OG oxygenases. With further research, we have also found that the function of 2OG oxygenases may be related to their polarity and hydrophobicity, which will help the follow-up study on the catalytic mechanism of 2OG oxygenases and the way they interact with the substrate. Based on the model we built, a user-friendly web server was established and can be friendly accessed at http://bioinfor.imu.edu.cn/ogferaac.

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Section: Predictive Performance Of Different Reducing Amino Acid Clustermentioning

confidence: 99%

Identification of Disease-Related 2-Oxoglutarate/Fe (II)-Dependent Oxygenase Based on Reduced Amino Acid Cluster Strategy

Zhou

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…In conclusion, we identified incomplete activation of transcription pathways and massive dysregulation of genes related to transcription pathway in NTA embryos. Then, the GRNs indicated that crucial factors responsible for transcription play a coordinated role in epigenome erasure and pluripotency regulation during normal embryo development [ 44 , 45 , 46 , 47 ]. However, in NTA embryos, predicted target genes of transcription pathways were varying in degrees of inhibition and showed a defect in synergy.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Transfer Arrest Embryos Show Massive Dysregulation of Genes Involved in Transcription Pathways

Long

et al. 2021

IJMS

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Somatic cell nuclear transfer (SCNT) technology can reprogram terminally differentiated cell nuclei into a totipotent state. However, the underlying molecular barriers of SCNT embryo development remain incompletely elucidated. Here, we observed that transcription-related pathways were incompletely activated in nuclear transfer arrest (NTA) embryos compared to normal SCNT embryos and in vivo fertilized (WT) embryos, which hinders the development of SCNT embryos. We further revealed the transcription pathway associated gene regulatory networks (GRNs) and found the aberrant transcription pathways can lead to the massive dysregulation of genes in NTA embryos. The predicted target genes of transcription pathways contain a series of crucial factors in WT embryos, which play an important role in catabolic process, pluripotency regulation, epigenetic modification and signal transduction. In NTA embryos, however, these genes were varying degrees of inhibition and show a defect in synergy. Overall, our research found that the incomplete activation of transcription pathways is another potential molecular barrier for SCNT embryos besides the incomplete reprogramming of epigenetic modifications, broadening the understanding of molecular mechanism of SCNT embryonic development.

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“…9 homolog üyeden meydana gelmektedir. Bu aile üyelerinin en önemli özelliği geniş spektrumlu substrat seçiciliğidir 30 .…”

Section: Alkbh Ailesi (α-Ketoglutarat Bağımlı Hidroksilazlar)unclassified

“…TET proteinlerinin substratlarını hidroksile edebilmesi için ALKBH enzimlerinde olduğu gibi Fe (II) ve αketoglutarat gibi kofaktörler gerekmektedir. Hem TET1 hem de TET3 proteinleri ALKBH'dan farklı olarak DNA'nın metilasyon durumunu ayırt edebilen N-terminalinde bir CXXC çinko bağlama alanı içerir [30][31] .…”

Section: Tet (On-on Bir Translokasyon Dioksijenaz Ailesi)unclassified

Demethylation of Nucleobases and Current Developments

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2021

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Epigenetics is defined as changes in gene function that do not change the DNA sequence, but result in changes in the functions and regulation mechanisms of DNA, proteins and RNAs. Studies conducted in the field of epigenetics with the developing technology in recent years have enabled us to discover its important effects on humans and to understand its relationship with diseases. Many diseases occur as a result of excessive increase / suppression of the expression of genes by error or irregularity in the regulation of epigenetic mechanisms. The epigenetic mechanism that has been studied a lot and the most known epigenetic mechanism is DNA and RNA methylation. In addition to methylations, molecular-level research on DNA and RNA demethylation processes has gained great importance in understanding and evaluating epigenetic disease mechanisms.

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Multi-substrate selectivity based on key loops and non-homologous domains: new insight into ALKBH family

Cited by 54 publications

References 160 publications

Identification of Disease-Related 2-Oxoglutarate/Fe (II)-Dependent Oxygenase Based on Reduced Amino Acid Cluster Strategy

Identification of Disease-Related 2-Oxoglutarate/Fe (II)-Dependent Oxygenase Based on Reduced Amino Acid Cluster Strategy

Nuclear Transfer Arrest Embryos Show Massive Dysregulation of Genes Involved in Transcription Pathways

Demethylation of Nucleobases and Current Developments

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