Modeling the Embrace of a Mutator: APOBEC Selection of Nucleic Acid Ligands

Salter, Jason D.; Smith, Harold C.

doi:10.1016/j.tibs.2018.04.013

Cited by 59 publications

(65 citation statements)

References 137 publications

(257 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The whole DNA is in a straight‐line binding groove, similar to that predicted by Chen, et al . Compared to other A3‐DNA complexes (Figure S6), the CCC binding mode of 3′‐end of DNA in A3G‐PrA complex is also included in A3A‐DNA and A3G‐CTD2*‐DNA complexes, while the TCC binding mode of 3′‐end of DNA in A3G‐PrB complex is almost identical to those observed in chimeric A3B‐DNA complex and in rA3G‐CD1 in complex with DNA . In contrast, the position of DNA in A3F‐DNA complex is much far away from the catalytic center, different from those in A3G‐PrA, A3G‐PrB, A3A‐DNA and A3B‐DNA complexes.…”

Section: Figuresupporting

confidence: 91%

“…The whole DNA is in ak inked-line binding groove, similar to the one predicted by Holden, et al [29] The TCC orientation was observed in A3G-PrBc omplex, locating between A3G-CD2l oop 3a nd a3h elix or loop 5. The whole DNA is in a straight-line binding groove, similart ot hat predicted by Chen, et al [23,43] Compared to other A3-DNA complexes ( Figure S6), [44] the CCC binding mode of 3'-end of DNA in A3G-PrA complex is also included in A3A-DNA and A3G-CTD2*-DNA com-plexes, [34,35] while the TCC binding mode of 3'-end of DNA in A3G-PrBc omplex is almost identicalt ot hose observed in chimeric A3B-DNAc omplex [35] and in rA3G-CD1 in complex with DNA. [27] In contrast, the positiono fD NA in A3F-DNA complex is much far away from the catalytic center, [36] different from those in A3G-PrA,A 3G-PrB, A3A-DNA andA 3B-DNAc omplexes.…”

supporting

confidence: 83%

See 1 more Smart Citation

Structural Investigations on the Interactions between Cytidine Deaminase Human APOBEC3G and DNA

Yan

Lan

Wang

et al. 2019

Chemistry An Asian Journal

View full text Add to dashboard Cite

Human APOBEC3G (A3G) inhibits the replication of human immunodeficiency virus‐1 by deaminating cytidine at the 3′‐end in the target motif 5′‐CCC‐3′ in viral cDNA during reverse transcription. It in vitro deaminates two consecutive cytidines in a 3′‐>5′ order. Although a crystal structure of the A3G catalytic domain (A3G‐CD2) with DNA was reported, it is unknown why residues involved in enzymatic reaction are distributed widely. Here, we introduced an iodine atom into the C‐5 position of cytidine (dC6I) in DNA 5′‐ATTC4C5C6IA7ATT‐3′ (TCCC6I). It switches the deamination sequence preference from CCC to TCC, although small dC6I deamination was observed. Solution structures of A3G‐CD2 in complexes with products DNA TCUC6I and TCUU6I indicate that the substrate DNA binds A3G‐CD2 in TCC and CCC modes. The dC6 deamination correlates with the 4th base type. The CCC mode favours dC6 deamination, while the TCC mode results in dC5 deamination. These studies present an extensive basis to design inhibitors to impede viral evolvability.

show abstract

Section: Figuresupporting

confidence: 91%

supporting

confidence: 83%

Structural Investigations on the Interactions between Cytidine Deaminase Human APOBEC3G and DNA

Yan

Lan

Wang

et al. 2019

Chemistry An Asian Journal

View full text Add to dashboard Cite

show abstract

“…Among the processes involved is RNA and DNA editing mediated by endogenous deaminases. Two different deaminase families are present in mammalian species: the ADARs target double stranded RNA (dsRNA) for deamination of Adenines into Inosines (A-to-I) (3,4), and the APOBECs deaminate Cytosines into Uracils (C-to-U) on singlestranded nucleic acids (ssDNA and ssRNA) (5,6). ADARs interfere with viral infections directly 10 -through hypermutation of viral RNA-and indirectly, through modulation of the intracellular response (7)(8)(9)(10)(11)(12).…”

Section: Main Textmentioning

confidence: 99%

Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2

Giorgio

Martignano

Torcia

et al. 2020

Preprint

View full text Add to dashboard Cite

The 2019-nCoV outbreak has become a global health risk. Editing by host deaminases is an innate restriction process to counter viruses, and it is not yet known whether it operates against 15 coronaviruses. Here we analyze RNA sequences from bronchoalveolar lavage fluids derived from two Wuhan patients. We identify nucleotide changes that may be signatures of RNA editing:Adenosine-to-Inosine changes from ADAR deaminases and Cytosine-to-Uracil changes from APOBEC ones. A mutational analysis of genomes from different strains of human-hosted Coronaviridae reveals patterns similar to the RNA editing pattern observed in the 2019-nCoV 20 transcriptomes. Our results suggest that both APOBECs and ADARs are involved in Coronavirus genome editing, a process that may shape the fate of both virus and patient.

show abstract

“…The hallmark activity of the APOBEC family of enzymes is catalyzing a zinc ion‐mediated hydrolytic deamination of 2'‐deoxycytidine to 2'‐deoxyuridine in single‐stranded (ss)DNA [reviewed by Refs. ]. In addition to AID and APOBEC1, human cells have the potential to express up to seven different APOBEC3 (A3) enzymes (A3A‐D, A3F‐H).…”

Section: Introductionmentioning

confidence: 99%

Active site plasticity and possible modes of chemical inhibition of the human DNA deaminase APOBEC3B

et al. 2019

View full text Add to dashboard Cite

The single-stranded DNA cytosine deaminase APOBEC3B (A3B) functions in innate immunity against viruses, but it is also strongly implicated in eliciting mutations in cancer genomes. Because of the critical role of A3B in promoting virus and tumor evolution, small molecule inhibitors are desirable. However, there is no reported structure for any of the APOBEC3-family enzymes in complex with a small molecule bound in the active site, which hampers the development of small molecules targeting A3B. Here we report high-resolution structures of an active A3B catalytic domain chimera with loop 7 residues exchanged with those from the corresponding region of APOBEC3G (A3G). The structures reveal novel open conformations lacking the catalytically essential zinc ion, with the highly conserved active site residues extensively rearranged. These inactive conformations are stabilized by 2-pyrimidone or an iodide ion bound in the active site. Molecular dynamics simulations corroborate the remarkable plasticity of the engineered active site and identify key interactions that stabilize the native A3B active site. These data provide insights into A3B active site dynamics and suggest possible modes of its inhibition by small molecules, which would aid in rational design of selective A3B inhibitors for constraining virus and tumor evolution. K E Y W O R D Sactive site plasticity, APOBEC3B, cytosine deaminase, DNA mutation, enzymes, molecular dynamics simulations, protein structure, small molecule, x-ray crystallography, zinc ion 50 | SHI et al

show abstract

Modeling the Embrace of a Mutator: APOBEC Selection of Nucleic Acid Ligands

Cited by 59 publications

References 137 publications

Structural Investigations on the Interactions between Cytidine Deaminase Human APOBEC3G and DNA

Structural Investigations on the Interactions between Cytidine Deaminase Human APOBEC3G and DNA

Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2

Active site plasticity and possible modes of chemical inhibition of the human DNA deaminase APOBEC3B

Contact Info

Product

Resources

About