| Structural highlights
Function
DPOLX_ASFB7 Error-prone polymerase lacking a proofreading 3'-5' exonuclease which plays a role in viral DNA repair. Specifically binds intermediates in the single-nucleotide base-excision repair process. Also catalyzes DNA polymerization with low nucleotide-insertion fidelity. Together with the viral DNA ligase, fills the single nucleotide gaps generated by the AP endonuclease.[1] [2]
Publication Abstract from PubMed
In addition to storage of genetic information, DNA can also catalyze various reactions. RNA-cleaving DNAzymes are the catalytic DNAs discovered the earliest, and they can cleave RNAs in a sequence-specific manner. Owing to their great potential in medical therapeutics, virus control, and gene silencing for disease treatments, RNA-cleaving DNAzymes have been extensively studied; however, the mechanistic understandings of their substrate recognition and catalysis remain elusive. Here, we report three catalytic form 8-17 DNAzyme crystal structures. 8-17 DNAzyme adopts a V-shape fold, and the Pb(2+) cofactor is bound at the pre-organized pocket. The structures with Pb(2+) and the modification at the cleavage site captured the pre-catalytic state of the RNA cleavage reaction, illustrating the unexpected Pb(2+)-accelerated catalysis, intrinsic tertiary interactions, and molecular kink at the active site. Our studies reveal that DNA is capable of forming a compacted structure and that the functionality-limited bio-polymer can have a novel solution for a functional need in catalysis.
Crystal structure of an RNA-cleaving DNAzyme.,Liu H, Yu X, Chen Y, Zhang J, Wu B, Zheng L, Haruehanroengra P, Wang R, Li S, Lin J, Li J, Sheng J, Huang Z, Ma J, Gan J Nat Commun. 2017 Dec 8;8(1):2006. doi: 10.1038/s41467-017-02203-x. PMID:29222499[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Garcia-Escudero R, Garcia-Diaz M, Salas ML, Blanco L, Salas J. DNA polymerase X of African swine fever virus: insertion fidelity on gapped DNA substrates and AP lyase activity support a role in base excision repair of viral DNA. J Mol Biol. 2003 Mar 7;326(5):1403-12. PMID:12595253
- ↑ Showalter AK, Byeon IJ, Su MI, Tsai MD. Solution structure of a viral DNA polymerase X and evidence for a mutagenic function. Nat Struct Biol. 2001 Nov;8(11):942-6. PMID:11685239 doi:10.1038/nsb1101-942
- ↑ Liu H, Yu X, Chen Y, Zhang J, Wu B, Zheng L, Haruehanroengra P, Wang R, Li S, Lin J, Li J, Sheng J, Huang Z, Ma J, Gan J. Crystal structure of an RNA-cleaving DNAzyme. Nat Commun. 2017 Dec 8;8(1):2006. doi: 10.1038/s41467-017-02203-x. PMID:29222499 doi:http://dx.doi.org/10.1038/s41467-017-02203-x
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