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Hydrolase PDB id
1ktg
Jmol
Contents
Protein chains
137 a.a. *
Ligands
PO4 ×2
_OH ×2
AMP
Metals
_MG ×9
Waters ×304
* Residue conservation analysis
PDB id:
1ktg
Name: Hydrolase
Title: Crystal structure of a c. Elegans ap4a hydrolase binary complex
Structure: Diadenosine tetraphosphate hydrolase. Chain: a, b. Engineered: yes
Source: Caenorhabditis elegans. Organism_taxid: 6239. Gene: y37h9a.6. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.80Å     R-factor:   0.190     R-free:   0.223
Authors: S.Bailey,S.E.Sedelnikova,G.M.Blackburn,H.M.Abdelghany, P.J.Baker,A.G.Mclennan,J.B.Rafferty
Key ref:
S.Bailey et al. (2002). The crystal structure of diadenosine tetraphosphate hydrolase from Caenorhabditis elegans in free and binary complex forms. Structure, 10, 589-600. PubMed id: 11937063 DOI: 10.1016/S0969-2126(02)00746-3
Date:
16-Jan-02     Release date:   08-May-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9U2M7  (AP4A_CAEEL) -  Bis(5'-nucleosyl)-tetraphosphatase [asymmetrical]
Seq:
Struc: 		138 a.a.
138 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cellular_component   1 term 
  Biological process     induction of apoptosis   1 term 
  Biochemical function     nucleotide binding     5 terms  

 

 
DOI no: 10.1016/S0969-2126(02)00746-3 Structure 10:589-600 (2002)
PubMed id: 11937063  
 
 
The crystal structure of diadenosine tetraphosphate hydrolase from Caenorhabditis elegans in free and binary complex forms.
S.Bailey, S.E.Sedelnikova, G.M.Blackburn, H.M.Abdelghany, P.J.Baker, A.G.McLennan, J.B.Rafferty.
 
  ABSTRACT  
 
The crystal structure of C. elegans Ap(4)A hydrolase has been determined for the free enzyme and a binary complex at 2.0 A and 1.8 A, respectively. Ap(4)A hydrolase has a key role in regulating the intracellular Ap(4)A levels and hence potentially the cellular response to metabolic stress and/or differentiation and apoptosis via the Ap(3)A/Ap(4)A ratio. The structures reveal that the enzyme has the mixed alpha/beta fold of the Nudix family and also show how the enzyme binds and locates its substrate with respect to the catalytic machinery of the Nudix motif. These results suggest how the enzyme can catalyze the hydrolysis of a range of related dinucleoside tetraphosphate, but not triphosphate, compounds through precise orientation of key elements of the substrate.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. The Binary Complex(A) The electron density map for the AMP moiety in the final 2Fo-Fc map contoured at 1s.(B) An Fo-Fc electron density omit map for the bound anion at the P4-phosphate site and associated magnesium cations.(C and D) Orthogonal views of the substrate binding cleft of the enzyme showing the location of the bound AMP moiety and the anion at the P4 phosphate site (see text). The protein is shown with a helices and b strands as cylinders and arrows, respectively, and the AMP and P4 anions are shown in all-atom representation.(E) A stereo view of the binding site for the AMP moiety with the key interacting residues (see text) shown. Hydrogen bonds/ion pairs are shown as black lines. Figures produced using WebLabViewer V4.0 and TURBO-FRODO (A. Roussel et al., 1997, XV IUCr Congress, abstract).
 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 589-600) copyright 2002.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20124691 J.Jeyakanthan, S.P.Kanaujia, Y.Nishida, N.Nakagawa, S.Praveen, A.Shinkai, S.Kuramitsu, S.Yokoyama, and K.Sekar (2010).
Free and ATP-bound structures of Ap4A hydrolase from Aquifex aeolicus V5.
  Acta Crystallogr D Biol Crystallogr, 66, 116-124.
PDB codes: 3i7u 3i7v
19864691 T.Nakamura, S.Meshitsuka, S.Kitagawa, N.Abe, J.Yamada, T.Ishino, H.Nakano, T.Tsuzuki, T.Doi, Y.Kobayashi, S.Fujii, M.Sekiguchi, and Y.Yamagata (2010).
Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base.
  J Biol Chem, 285, 444-452.
PDB codes: 3a6s 3a6t 3a6u 3a6v
19210543 A.Guranowski, E.Starzyńska, M.Pietrowska-Borek, D.Rejman, and G.M.Blackburn (2009).
Novel diadenosine polyphosphate analogs with oxymethylene bridges replacing oxygen in the polyphosphate chain: potential substrates and/or inhibitors of Ap4A hydrolases.
  FEBS J, 276, 1546-1553.  
19604474 N.Huang, J.De Ingeniis, L.Galeazzi, C.Mancini, Y.D.Korostelev, A.B.Rakhmaninova, M.S.Gelfand, D.A.Rodionov, N.Raffaelli, and H.Zhang (2009).
Structure and function of an ADP-ribose-dependent transcriptional regulator of NAD metabolism.
  Structure, 17, 939-951.
PDB code: 3gz8
18512963 G.W.Buchko, O.Litvinova, H.Robinson, A.F.Yakunin, and M.A.Kennedy (2008).
Functional and structural characterization of DR_0079 from Deinococcus radiodurans, a novel Nudix hydrolase with a preference for cytosine (deoxy)ribonucleoside 5'-Di- and triphosphates.
  Biochemistry, 47, 6571-6582.
PDB code: 2o5f
18445629 M.Coseno, G.Martin, C.Berger, G.Gilmartin, W.Keller, and S.Doublié (2008).
Crystal structure of the 25 kDa subunit of human cleavage factor Im.
  Nucleic Acids Res, 36, 3474-3483.
PDB codes: 3bap 3bho
18280238 M.V.Deshmukh, B.N.Jones, D.U.Quang-Dang, J.Flinders, S.N.Floor, C.Kim, J.Jemielity, M.Kalek, E.Darzynkiewicz, and J.D.Gross (2008).
mRNA decapping is promoted by an RNA-binding channel in Dcp2.
  Mol Cell, 29, 324-336.
PDB code: 2jvb
17344088 L.Winward, W.G.Whitfield, T.J.Woodman, A.G.McLennan, and S.T.Safrany (2007).
Characterisation of a bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) from Drosophila melanogaster.
  Int J Biochem Cell Biol, 39, 943-954.  
16441668 A.Guranowski, E.Starzyńska, M.Pietrowska-Borek, J.Jemielity, J.Kowalska, E.Darzynkiewicz, M.J.Thompson, and G.M.Blackburn (2006).
Methylene analogues of adenosine 5'-tetraphosphate. Their chemical synthesis and recognition by human and plant mononucleoside tetraphosphatases and dinucleoside tetraphosphatases.
  FEBS J, 273, 829-838.  
16900379 D.I.Fisher, J.L.Cartwright, and A.G.McLennan (2006).
Characterization of the Mn2+-stimulated (di)adenosine polyphosphate hydrolase encoded by the Deinococcus radiodurans DR2356 nudix gene.
  Arch Microbiol, 186, 415-424.  
16341225 M.She, C.J.Decker, N.Chen, S.Tumati, R.Parker, and H.Song (2006).
Crystal structure and functional analysis of Dcp2p from Schizosaccharomyces pombe.
  Nat Struct Mol Biol, 13, 63-70.
PDB code: 2a6t
17006950 Q.H.Wang, W.X.Hu, W.Gao, and R.C.Bi (2006).
Crystal structure of the diadenosine tetraphosphate hydrolase from Shigella flexneri 2a.
  Proteins, 65, 1032-1035.
PDB code: 2dfj
15772762 J.D.Swarbrick, S.Buyya, D.Gunawardana, J.I.Fletcher, K.Branson, B.Smith, S.Pepe, A.G.McLennan, K.R.Gayler, and P.R.Gooley (2005).
1H, 13C, and 15N resonance assignments of the 17 kDa Ap4A hydrolase from Homo sapiens in the presence and absence of ATP.
  J Biomol NMR, 31, 181-182.  
15596429 J.D.Swarbrick, S.Buyya, D.Gunawardana, K.R.Gayler, A.G.McLennan, and P.R.Gooley (2005).
Structure and substrate-binding mechanism of human Ap4A hydrolase.
  J Biol Chem, 280, 8471-8481.
PDB codes: 1xsa 1xsb 1xsc
15162484 G.W.Buchko, S.Ni, S.R.Holbrook, and M.A.Kennedy (2004).
Solution structure of hypothetical Nudix hydrolase DR0079 from extremely radiation-resistant Deinococcus radiodurans bacterium.
  Proteins, 56, 28-39.
PDB code: 1q27
15274914 S.B.Gabelli, M.A.Bianchet, H.F.Azurmendi, Z.Xia, V.Sarawat, A.S.Mildvan, and L.M.Amzel (2004).
Structure and mechanism of GDP-mannose glycosyl hydrolase, a Nudix enzyme that cleaves at carbon instead of phosphorus.
  Structure, 12, 927-935.
PDB code: 1rya
15024014 T.Iwai, S.Kuramitsu, and R.Masui (2004).
The Nudix hydrolase Ndx1 from Thermus thermophilus HB8 is a diadenosine hexaphosphate hydrolase with a novel activity.
  J Biol Chem, 279, 21732-21739.  
12657797 E.L.Holbrook, U.Schulze-Gahmen, G.W.Buchko, S.Ni, M.A.Kennedy, and S.R.Holbrook (2003).
Purification, crystallization and preliminary X-ray analysis of two nudix hydrolases from Deinococcus radiodurans.
  Acta Crystallogr D Biol Crystallogr, 59, 737-740.  
12475970 H.M.Abdelghany, S.Bailey, G.M.Blackburn, J.B.Rafferty, and A.G.McLennan (2003).
Analysis of the catalytic and binding residues of the diadenosine tetraphosphate pyrophosphohydrolase from Caenorhabditis elegans by site-directed mutagenesis.
  J Biol Chem, 278, 4435-4439.  
12370170 D.I.Fisher, S.T.Safrany, P.Strike, A.G.McLennan, and J.L.Cartwright (2002).
Nudix hydrolases that degrade dinucleoside and diphosphoinositol polyphosphates also have 5-phosphoribosyl 1-pyrophosphate (PRPP) pyrophosphatase activity that generates the glycolytic activator ribose 1,5-bisphosphate.
  J Biol Chem, 277, 47313-47317.  
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.