7d3w

Non-specific and specific interactions work cooperatively to promote cytidine deamination catalyzed by APOBEC3A

spinqualitylabelsall models 7d3w Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7d3w is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ABC3A_HUMAN DNA deaminase (cytidine deaminase) with restriction activity against viruses, foreign DNA and mobility of retrotransposons. Exhibits antiviral activity against adeno-associated virus (AAV) and human T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons. Selectively targets single-stranded DNA and can deaminate both methylcytosine and cytosine in foreign DNA. Can induce somatic hypermutation in the nuclear and mitochondrial DNA. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation. Publication Abstract from PubMed APOBEC3A (A3A) deaminates deoxycytidine in target motif TC in a single-stranded DNA (we termed it as TC DNA), which mortally mutates viral pathogens and immunoglobulins, and leads to the diversification and lethality of cancers. The crystal structure of A3A-DNA revealed a unique U-shaped recognition mode of target base dC(0) . However, when TC DNA was titrated into (15) N-labeled A3A solution, we observed two sets of (1) H-(15) N cross-peaks of A3A in HSQC spectra, and two sets of (1) H-(1) H cross-peaks of DNA in two-dimensional (13) C,(15) N-filtered TOCSY spectra, indicating two different kinds of conformers of either A3A or TC DNA existing in solution. Here, mainly by NMR, we demonstrated that one DNA conformer interacted with one A3A conformer, forming a specific complex A3A(S) -DNA(S) in a way almost similar to that observed in the reported crystal A3A-DNA structure, where dC(0) inserted into zinc ion binding center. While the other DNA conformer bound with another A3A conformer, but dC(0) did not extend into the zinc-binding pocket, forming a nonspecific A3A(NS) -DNA(NS) complex. The NMR solution structure implied three sites Asn(61) , His(182) and Arg(189) were necessary to DNA recognition. These observations indicate a distinctive way from that reported in X-ray crystal structure, suggesting an unexpected mode of deaminase APOBEC3A to identify target motif TC in DNA in solution. Two different kinds of interaction modes of deaminase APOBEC3A with single-stranded DNA in solution detected by nuclear magnetic resonance.,Liu Y, Lan W, Wang C, Cao C Protein Sci. 2022 Feb;31(2):443-453. doi: 10.1002/pro.4242. Epub 2021 Nov 26. PMID:34792260 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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