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Hydrolase PDB id
2i4i
Jmol
Contents
Protein chain
408 a.a. *
Ligands
AMP
Waters ×199
* Residue conservation analysis
PDB id:
2i4i
Name: Hydrolase
Title: Crystal structure of human dead-box RNA helicase ddx3x
Structure: Atp-dependent RNA helicase ddx3x. Chain: a. Synonym: dead box protein 3, x- chromosomal, helicase-like hlp2, dead box, x isoform. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ddx3x. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.20Å     R-factor:   0.189     R-free:   0.218
Authors: M.Hogbom,T.Karlberg,C.Arrowsmith,H.Berglund,R.D.Busam,R.Coll A.Edwards,M.Ehn,S.Flodin,A.Flores,S.Graslund,B.M.Hallberg, M.Hammarstrom,I.Johansson,T.Kotenyova,A.Magnusdottir,P.Nils P.Nordlund,T.Nyman,D.Ogg,C.Persson,J.Sagemark,P.Stenmark, M.Sundstrom,A.G.Thorsell,J.Uppenberg,S.Van Den Berg,K.Walld J.Weigelt,M.Welin,L.Holmberg-Schiavone,Structural Genomics Consortium (Sgc)
Key ref:
M.Högbom et al. (2007). Crystal structure of conserved domains 1 and 2 of the human DEAD-box helicase DDX3X in complex with the mononucleotide AMP. J Mol Biol, 372, 150-159. PubMed id: 17631897 DOI: 10.1016/j.jmb.2007.06.050
Date:
22-Aug-06     Release date:   05-Sep-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O00571  (DDX3X_HUMAN) -  ATP-dependent RNA helicase DDX3X
Seq:
Struc: 		 
Seq:
Struc: 		662 a.a.
408 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.3.6.4.13  - Rna helicase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O = ADP + phosphate
ATP
 + H(2)O
 =
ADP
Bound ligand (Het Group name = AMP)
matches with 85.19% similarity 		+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     nucleic acid binding     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2007.06.050 J Mol Biol 372:150-159 (2007)
PubMed id: 17631897  
 
 
Crystal structure of conserved domains 1 and 2 of the human DEAD-box helicase DDX3X in complex with the mononucleotide AMP.
M.Högbom, R.Collins, S.van den Berg, R.M.Jenvert, T.Karlberg, T.Kotenyova, A.Flores, G.B.Karlsson Hedestam, L.H.Schiavone.
 
  ABSTRACT  
 
DExD-box helicases are involved in all aspects of cellular RNA metabolism. Conserved domains 1 and 2 contain nine signature motifs that are responsible for nucleotide binding, RNA binding and ATP hydrolysis. The human DEAD-box helicase DDX3X has been associated with several different cellular processes, such as cell-growth control, mRNA transport and translation, and is suggested to be essential for the export of unspliced/partially spliced HIV mRNAs from the nucleus to the cytoplasm. Here, the crystal structure of conserved domains 1 and 2 of DDX3X, including a DDX3-specific insertion that is not generally found in human DExD-box helicases, is presented. The N-terminal domain 1 and the C-terminal domain 2 both display RecA-like folds comprising a central beta-sheet flanked by alpha-helices. Interestingly, the DDX3X-specific insertion forms a helical element that extends a highly positively charged sequence in a loop, thus increasing the RNA-binding surface of the protein. Surprisingly, although DDX3X was crystallized in the presence of a large excess of ADP or the slowly hydrolyzable ATP analogue ATPgammaS the contaminant AMP was seen in the structure. A fluorescent-based stability assay showed that the thermal stability of DDX3X was increased by the mononucleotide AMP but not by ADP or ATPgammaS, suggesting that DDX3X is stabilized by AMP and elucidating why AMP was found in the nucleotide-binding pocket.
 
  Selected figure(s)  
 
Figure 3.
 Figure 4.
Figure 4. (a) Superposition of the loop region in the vicinity of the DDX3-specific insertion, coloring as in Figure 2(b) and mapped on the DDX3X(V168-G582) structure (blue). Positively charged residues in the extended loop in DDX3X(V168-G582) are shown as sticks. (b) Surface contact potential representation of an RNA-bound model of DDX3X(V168-G582) (based on the Drosophila VASA structure). The extended loop creates an elongated, positively charged cavity positioned close to one end of the short RNA ligand.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 372, 150-159) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21391900 J.Strohmeier, I.Hertel, U.Diederichsen, M.G.Rudolph, and D.Klostermeier (2011).
Changing nucleotide specificity of the DEAD-box helicase Hera abrogates communication between the Q-motif and the P-loop.
  Biol Chem, 392, 357-369.
PDB codes: 3mwj 3mwk 3mwl 3nbf 3nej
20309906 O.Mulhern, and A.G.Bowie (2010).
Unexpected roles for DEAD-box protein 3 in viral RNA sensing pathways.
  Eur J Immunol, 40, 933-935.  
  20941364 P.Schütz, T.Karlberg, S.van den Berg, R.Collins, L.Lehtiö, M.Högbom, L.Holmberg-Schiavone, W.Tempel, H.W.Park, M.Hammarström, M.Moche, A.G.Thorsell, and H.Schüler (2010).
Comparative structural analysis of human DEAD-box RNA helicases.
  PLoS One, 5, 0.
PDB codes: 2g9n 2p6n 2pl3 2rb4 3b7g 3ber 3bor 3dkp 3fe2 3iuy 3ly5
20438638 T.C.Chang, and W.S.Liu (2010).
The molecular evolution of PL10 homologs.
  BMC Evol Biol, 10, 127.  
19050012 D.Klostermeier, and M.G.Rudolph (2009).
A novel dimerization motif in the C-terminal domain of the Thermus thermophilus DEAD box helicase Hera confers substantial flexibility.
  Nucleic Acids Res, 37, 421-430.
PDB codes: 3eaq 3ear 3eas
19285948 F.Tritschler, J.E.Braun, A.Eulalio, V.Truffault, E.Izaurralde, and O.Weichenrieder (2009).
Structural basis for the mutually exclusive anchoring of P body components EDC3 and Tral to the DEAD box protein DDX6/Me31B.
  Mol Cell, 33, 661-668.
PDB codes: 2wax 2way
19820710 H.W.Wang, C.Noland, B.Siridechadilok, D.W.Taylor, E.Ma, K.Felderer, J.A.Doudna, and E.Nogales (2009).
Structural insights into RNA processing by the human RISC-loading complex.
  Nat Struct Mol Biol, 16, 1148-1153.  
19747077 M.Hilbert, A.R.Karow, and D.Klostermeier (2009).
The mechanism of ATP-dependent RNA unwinding by DEAD box proteins.
  Biol Chem, 390, 1237-1250.  
19002498 M.Singh, K.K.Srivastava, and S.M.Bhattacharya (2009).
Molecular cloning and characterization of a novel immunoreactive ATPase/RNA helicase in human filarial parasite Brugia malayi.
  Parasitol Res, 104, 753-761.  
19244245 R.Collins, T.Karlberg, L.Lehtiö, P.Schütz, S.van den Berg, L.G.Dahlgren, M.Hammarström, J.Weigelt, and H.Schüler (2009).
The DEXD/H-box RNA Helicase DDX19 Is Regulated by an {alpha}-Helical Switch.
  J Biol Chem, 284, 10296-10300.
PDB codes: 3ews 3g0h
19913487 S.Oda, M.Schröder, and A.R.Khan (2009).
Structural basis for targeting of human RNA helicase DDX3 by poxvirus protein K7.
  Structure, 17, 1528-1537.
PDB code: 3jrv
18628297 C.S.Lee, A.P.Dias, M.Jedrychowski, A.H.Patel, J.L.Hsu, and R.Reed (2008).
Human DDX3 functions in translation and interacts with the translation initiation factor eIF3.
  Nucleic Acids Res, 36, 4708-4718.  
18583960 D.Soulat, T.Bürckstümmer, S.Westermayer, A.Goncalves, A.Bauch, A.Stefanovic, O.Hantschel, K.L.Bennett, T.Decker, and G.Superti-Furga (2008).
The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response.
  EMBO J, 27, 2135-2146.  
18164611 H.Le Hir, and G.R.Andersen (2008).
Structural insights into the exon junction complex.
  Curr Opin Struct Biol, 18, 112-119.  
18332124 J.Banroques, O.Cordin, M.Doère, P.Linder, and N.K.Tanner (2008).
A conserved phenylalanine of motif IV in superfamily 2 helicases is required for cooperative, ATP-dependent binding of RNA substrates in DEAD-box proteins.
  Mol Cell Biol, 28, 3359-3371.  
18636090 M.Schröder, M.Baran, and A.G.Bowie (2008).
Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation.
  EMBO J, 27, 2147-2157.  
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.