2NBQ

NMR Structure of the C-Terminal Domain of human APOBEC3B

Summary for 2NBQ

• Entry DOI: 10.2210/pdb2nbq/pdb
• NMR Information: BMRB: 25985
• Descriptor: DNA dC->dU-editing enzyme APOBEC-3B, ZINC ION (2 entities in total)
• Functional Keywords: hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q9UH17
• Total number of polymer chains: 1
• Total formula weight: 24501.10

Authors

Byeon, I.L.,Byeon, C.,Gronenborn, A.M. (deposition date: 2016-03-09, release date: 2016-06-01, Last modification date: 2024-05-15)

Primary citation

Byeon, I.J.,Byeon, C.H.,Wu, T.,Mitra, M.,Singer, D.,Levin, J.G.,Gronenborn, A.M.
Nuclear Magnetic Resonance Structure of the APOBEC3B Catalytic Domain: Structural Basis for Substrate Binding and DNA Deaminase Activity.
Biochemistry, 55:2944-2959, 2016

PubMed Abstract: Human APOBEC3B (A3B) is a member of the APOBEC3 (A3) family of cytidine deaminases, which function as DNA mutators and restrict viral pathogens and endogenous retrotransposons. Recently, A3B was identified as a major source of genetic heterogeneity in several human cancers. Here, we determined the solution nuclear magnetic resonance structure of the catalytically active C-terminal domain (CTD) of A3B and performed detailed analyses of its deaminase activity. The core of the structure comprises a central five-stranded β-sheet with six surrounding helices, common to all A3 proteins. The structural fold is most similar to that of A3A and A3G-CTD, with the most prominent difference being found in loop 1. The catalytic activity of A3B-CTD is ∼15-fold lower than that of A3A, although both exhibit a similar pH dependence. Interestingly, A3B-CTD with an A3A loop 1 substitution had significantly increased deaminase activity, while a single-residue change (H29R) in A3A loop 1 reduced A3A activity to the level seen with A3B-CTD. This establishes that loop 1 plays an important role in A3-catalyzed deamination by precisely positioning the deamination-targeted C into the active site. Overall, our data provide important insights into the determinants of the activities of individual A3 proteins and facilitate understanding of their biological function.

PubMed: 27163633
DOI: 10.1021/acs.biochem.6b00382

Experimental method

SOLUTION NMR