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PDBsum entry 3c4t
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protein metals links
Hydrolase PDB id
3c4t

 

 

 

 

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Contents
Protein chain
242 a.a. *
Metals
_CD ×3
Waters ×6
* Residue conservation analysis
PDB id:
3c4t
Name: Hydrolase
Title: Structure of rnaseiiib and dsrna binding domains of mouse dicer
Structure: Endoribonuclease dicer. Chain: a. Fragment: rnaseiiib domain, dsrna binding domain (unp residues 1638- 1900). Synonym: double-strand-specific ribonuclease mdcr-1. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: dicer1, dicer, mdcr. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.80Å     R-factor:   0.236     R-free:   0.304
Authors: J.K.Lee,Z.Du,R.J.Tjhen,R.M.Stroud,T.L.James
Key ref:
Z.Du et al. (2008). Structural and biochemical insights into the dicing mechanism of mouse Dicer: a conserved lysine is critical for dsRNA cleavage. Proc Natl Acad Sci U S A, 105, 2391-2396. PubMed id: 18268334 DOI: 10.1073/pnas.0711506105
Date:
30-Jan-08     Release date:   19-Feb-08    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q8R418  (DICER_MOUSE) -  Endoribonuclease Dicer from Mus musculus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1916 a.a.
242 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.3.1.26.3  - ribonuclease Iii.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Endonucleolytic cleavage to 5'-phosphomonoester.

 

 
DOI no: 10.1073/pnas.0711506105 Proc Natl Acad Sci U S A 105:2391-2396 (2008)
PubMed id: 18268334  
 
 
Structural and biochemical insights into the dicing mechanism of mouse Dicer: a conserved lysine is critical for dsRNA cleavage.
Z.Du, J.K.Lee, R.Tjhen, R.M.Stroud, T.L.James.
 
  ABSTRACT  
 
Dicer, an RNase III enzyme, initiates RNA interference by processing precursor dsRNAs into mature microRNAs and small-interfering RNAs. It is also involved in loading and activation of the RNA-induced silencing complex. Here, we report the crystal structures of a catalytically active fragment of mouse Dicer, containing the RNase IIIb and dsRNA binding domains, in its apo and Cd(2+)-bound forms, at 1.68- and 2.8-A resolution, respectively. Models of this structure with dsRNA reveal that a lysine residue, highly conserved in Dicer RNase IIIa and IIIb domains and in Drosha RNase IIIb domains, has the potential to participate in the phosphodiester bond cleavage reaction by stabilizing the transition state and leaving group of the scissile bond. Mutational and enzymatic assays confirm the importance of this lysine in dsRNA cleavage, suggesting that this lysine represents a conserved catalytic residue of Dicers. The structures also reveals a approximately 45-aa region within the RNase IIIb domain that harbors an alpha-helix at the N-terminal half and a flexible loop at the C-terminal half, features not present in previously reported structures of homologous RNase III domains from either bacterial RNase III enzymes or Giardia Dicer. N-terminal residues of this alpha-helix have the potential to engage in minor groove interaction with dsRNA substrates.
 
  Selected figure(s)  
 
Figure 1.
A schematic representation of the three classes of RNase III enzymes. Protein domains are indicated as black rectangles. 		Figure 3.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22426548 P.W.Lau, K.Z.Guiley, N.De, C.S.Potter, B.Carragher, and I.J.MacRae (2012).
The molecular architecture of human Dicer.
  Nat Struct Mol Biol, 19, 436-440.  
20971974 B.Kolaczkowski, D.N.Hupalo, and A.D.Kern (2011).
Recurrent adaptation in RNA interference genes across the Drosophila phylogeny.
  Mol Biol Evol, 28, 1033-1042.  
21252293 K.Suk, J.Choi, Y.Suzuki, S.B.Ozturk, J.C.Mellor, K.H.Wong, J.L.MacKay, R.I.Gregory, and F.P.Roth (2011).
Reconstitution of human RNA interference in budding yeast.
  Nucleic Acids Res, 39, e43.  
20179251 S.Jaubert-Possamai, C.Rispe, S.Tanguy, K.Gordon, T.Walsh, O.Edwards, and D.Tagu (2010).
Expansion of the miRNA pathway in the hemipteran insect Acyrthosiphon pisum.
  Mol Biol Evol, 27, 979-987.  
19968858 W.M.Li, T.Barnes, and C.H.Lee (2010).
Endoribonucleases--enzymes gaining spotlight in mRNA metabolism.
  FEBS J, 277, 627-641.  
20167638 W.Salomon, K.Bulock, J.Lapierre, P.Pavco, T.Woolf, and J.Kamens (2010).
Modified dsRNAs that are not processed by Dicer maintain potency and are incorporated into the RISC.
  Nucleic Acids Res, 38, 3771-3779.  
19822745 C.Mui Chan, C.Zhou, J.S.Brunzelle, and R.H.Huang (2009).
Structural and biochemical insights into 2'-O-methylation at the 3'-terminal nucleotide of RNA by Hen1.
  Proc Natl Acad Sci U S A, 106, 17699-17704.
PDB codes: 3jwg 3jwh 3jwi 3jwj
19815526 K.L.Patrick, H.Shi, N.G.Kolev, K.Ersfeld, C.Tschudi, and E.Ullu (2009).
Distinct and overlapping roles for two Dicer-like proteins in the RNA interference pathways of the ancient eukaryote Trypanosoma brucei.
  Proc Natl Acad Sci U S A, 106, 17933-17938.  
19158786 M.Jinek, and J.A.Doudna (2009).
A three-dimensional view of the molecular machinery of RNA interference.
  Nature, 457, 405-412.  
19836333 P.W.Lau, C.S.Potter, B.Carragher, and I.J.MacRae (2009).
Structure of the human Dicer-TRBP complex by electron microscopy.
  Structure, 17, 1326-1332.  
19221817 Q.Liu, Y.Feng, and Z.Zhu (2009).
Dicer-like (DCL) proteins in plants.
  Funct Integr Genomics, 9, 277-286.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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