Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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Zalpha Z-DNA-binding domain in adenosine deaminases.

SMART accession number:	SM00550
Description:	Helix-turn-helix-containing domain. Also known as Zab.
Interpro abstract (IPR000607):	Double-stranded RNA-specific adenosine deaminase (EC 3.5) converts multiple adenosines to inosines and creates I/U mismatched base pairs in double-helical RNA substrates without apparent sequence specificity. DRADA has been found to modify adenosines in AU-rich regions more frequently, probably due to the relative ease of melting A/U base pairs compared to G/C base pairs. The protein functions to modify viral RNA genomes, and may be responsible for hypermutation of certain negative-stranded viruses. DRADA edits the mRNAs for the glutamate receptor subunits by site-selective adenosine deamination. The DRADA repeat is also found in viral E3 proteins, which contain a double-stranded RNA-binding domain.
GO function:	RNA binding (GO:0003723), double-stranded RNA adenosine deaminase activity (GO:0003726)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 88 Zalpha domains in 53 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a Zalpha domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with Zalpha domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Schade M et al.
  • The solution structure of the Zalpha domain of the human RNA editing enzyme ADAR1 reveals a prepositioned binding surface for Z-DNA.
  • Proc Natl Acad Sci U S A. 1999; 96: 12465-70
  • Display abstract

  • Double-stranded RNA deaminase I (ADAR1) contains the Z-DNA binding domain Zalpha. Here we report the solution structure of free Zalpha and map the interaction surface with Z-DNA, confirming roles previously assigned to residues by mutagenesis. Comparison with the crystal structure of the (Zalpha)(2)/Z-DNA complex shows that most Z-DNA contacting residues in free Zalpha are prepositioned to bind Z-DNA, thus minimizing the entropic cost of binding. Comparison with homologous (alpha+beta)helix-turn-helix/B-DNA complexes suggests that binding of Zalpha to B-DNA is disfavored by steric hindrance, but does not eliminate the possibility that related domains may bind to both B- and Z-DNA.

  • Schwartz T, Rould MA, Lowenhaupt K, Herbert A, Rich A
  • Crystal structure of the Zalpha domain of the human editing enzyme ADAR1 bound to left-handed Z-DNA.
  • Science. 1999; 284: 1841-5
  • Display abstract

  • The editing enzyme double-stranded RNA adenosine deaminase includes a DNA binding domain, Zalpha, which is specific for left-handed Z-DNA. The 2.1 angstrom crystal structure of Zalpha complexed to DNA reveals that the substrate is in the left-handed Z conformation. The contacts between Zalpha and Z-DNA are made primarily with the "zigzag" sugar-phosphate backbone, which provides a basis for the specificity for the Z conformation. A single base contact is observed to guanine in the syn conformation, characteristic of Z-DNA. Intriguingly, the helix-turn-helix motif, frequently used to recognize B-DNA, is used by Zalpha to contact Z-DNA.

  • Herbert A et al.
  • The Zalpha domain from human ADAR1 binds to the Z-DNA conformer of many different sequences.
  • Nucleic Acids Res. 1998; 26: 3486-93
  • Display abstract

  • Z-DNA, the left-handed conformer of DNA, is stabilized by the negative supercoiling generated during the movement of an RNA polymerase through a gene. Recently, we have shown that the editing enzyme ADAR1 (double-stranded RNA adenosine deaminase, type 1) has two Z-DNA binding motifs, Zalpha and Zbeta, the function of which is currently unknown. Here we show that a peptide containing the Zalpha motif binds with high affinity to Z-DNA as a dimer, that the binding site is no larger than 6 bp and that the Zalpha domain can flip a range of sequences, including d(TA)3, into the Z-DNAconformation. Evidence is also presented to show that Zalpha and Zbeta interact to form a functional DNA binding site. Studies with atomic force microscopy reveal that binding of Zalpha to supercoiled plasmids is associated with relaxation of the plasmid. Pronounced kinking of DNA is observed, and appears to be induced by binding of Zalpha. The results reported here support a model where the Z-DNA binding motifs target ADAR1 to regions of negative supercoiling in actively transcribing genes. In this situation, binding by Zalpha would be dependent upon the local level of negative superhelicity rather than the presence of any particular sequence.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 100.00 map00791 Atrazine degradation This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with Zalpha domain which could be assigned to a KEGG orthologous group, and not all proteins containing Zalpha domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of Zalpha domains in PDB

  PDB code	Main view	Title
  1j75		Crystal structure of the dna-binding domain zalpha of dlm-1 bound to z-dna
  1oyi		Solution structure of the z-dna binding domain of the vaccinia virus gene e3l
  1qbj		Crystal structure of the zalpha z-dna complex
  1qgp		Nmr structure of the z-alpha domain of adar1, 15 structures
  1sfu		Crystal structure of the viral zalpha domain bound to left- handed z-dna
  1xmk		The crystal structure of the zb domain from the rna editing enzyme adar1
  2acj		Crystal structure of the b/z junction containing dna bound to z-dna binding proteins
  2gxb		Crystal structure of the za domain bound to z-rna
  2heo		General structure-based approach to the design of protein ligands: application to the design of kv1.2 potassium channel blockers.
  3eyi		The crystal structure of the second z-dna binding domain of human dai (zbp1) in complex with z-dna
  3f21		Crystal structure of zalpha in complex with d(cacgtg)
  3f22		Crystal structure of zalpha in complex with d(cgtacg)
  3f23		Crystal structure of zalpha in complex with d(cggccg)

• Links (links to other resources describing this domain)

• INTERPRO	IPR000607

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