Evaluation of APOBEC3B Recognition Motifs by NMR Reveals Preferred Substrates | Zendy

Manjuan Liu | Zendy; Aurélie Mallinger | Zendy; Marcello Tortorici | Zendy; Yvette Newbatt | Zendy; Meirion Richards | Zendy; Amin Mirza | Zendy; Rob L. M. van Montfort | Zendy; Rosemary Burke | Zendy; Julian Blagg | Zendy; Teresa Kaserer | Zendy

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Evaluation of APOBEC3B Recognition Motifs by NMR Reveals Preferred Substrates

Author(s) -

Manjuan Liu,

Aurélie Mallinger,

Marcello Tortorici,

Yvette Newbatt,

Meirion Richards,

Amin Mirza,

Rob L. M. van Montfort,

Rosemary Burke,

Julian Blagg,

Teresa Kaserer

Publication year - 2018

Publication title -

acs chemical biology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.899

H-Index - 111

eISSN - 1554-8937

pISSN - 1554-8929

DOI - 10.1021/acschembio.8b00639

Subject(s) - substrate (aquarium) , substrate specificity , oligonucleotide , nucleotide , dna , deamination , computational biology , drug resistance , biology , biochemistry , enzyme , chemistry , genetics , gene , ecology

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.

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