5HP3: Human Adenosine Deaminase Acting On Dsrna (adar2) Bound To Dsrna Sequence Derived From S. Cerevisiae Bdf2 Gene With Ac Mismatch At Reaction Site

Adenosine deaminases acting on RNA (ADARs) are editing enzymes that convert adenosine to inosine in duplex RNA, a modification reaction with wide-ranging consequences in RNA function. Understanding of the ADAR reaction mechanism, the origin of editing-site selectivity, and the effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. Here we describe four crystal structures of the human ADAR2 deaminase domain bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis of the ADAR deaminase domain's dsRNA specificity, its base-flipping mechanism, and its nearest-neighbor preferences. In addition, we identified an ADAR2-specific RNA-binding loop near the enzyme active site, thus rationalizing differences in selectivity observed between different ADARs. Finally, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease.
PDB ID: 5HP3Download
MMDB ID: 138410
PDB Deposition Date: 2016/1/20
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 3.09  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 5HP3: trimeric; determined by author and by software (PISA)
Molecular Components in 5HP3
Label Count Molecule
Protein (1 molecule)
Double-stranded RNA-specific Editase 1(Gene symbol: ADARB1)
Molecule annotation
Nucleotides(2 molecules)
RNA (5'-r(*up*up*cp*cp*cp*cp*ap*cp*ap*up*up*(8az) P*gp*ap*cp*gp*up*up*cp*ap*gp*up*c)-3')
Molecule annotation
RNA (5'- R(*gp*ap*cp*up*gp*ap*ap*cp*gp*ap*cp*cp*ap*ap*up*gp*up*gp*gp*gp*gp*ap* A)-3')
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB