Evaluation of APOBEC3B Recognition Motifs by NMR Reveals Preferred Substrates.
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ICR Authors
Authors
Liu, M
Mallinger, A
Tortorici, M
Newbatt, Y
Richards, M
Mirza, A
van Montfort, RLM
Burke, R
Blagg, J
Kaserer, T
Mallinger, A
Tortorici, M
Newbatt, Y
Richards, M
Mirza, A
van Montfort, RLM
Burke, R
Blagg, J
Kaserer, T
Document Type
Journal Article
Date
2018-09-21
Date Accepted
Abstract
APOBEC3B (A3B) deamination activity on ssDNA is considered a contributing factor to tumor heterogeneity and drug resistance in a number of human cancers. Despite its clinical impact, little is known about A3B ssDNA substrate preference. We have used nuclear magnetic resonance to monitor the catalytic turnover of A3B substrates in real-time. This study reports preferred nucleotide sequences for A3B substrates, including optimized 4-mer oligonucleotides, and reveals a breadth of substrate recognition that includes DNA sequences known to be mutated in drug-resistant cancer clones. Our results are consistent with available clinical and structural data and may inform the design of substrate-based A3B inhibitors.
Citation
ACS chemical biology, 2018, 13 (9), pp. 2427 - 2432
Source Title
Publisher
AMER CHEMICAL SOC
ISSN
1554-8929
eISSN
1554-8937
Collections
Research Team
Hit Discovery & Structural Design