PDBsum entry 2jga

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Hydrolase PDB id
Protein chain
273 a.a. *
Waters ×15
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of human cytosolic 5'-nucleotidase iii in complex with phosphate and magnesium
Structure: Cytosolic 5'-nucleotidase iii. Chain: a. Fragment: residues 14-286. Synonym: cn-iii, pyrimidine 5'-nucleotidase 1, p5'n-1, p5n- uridine 5'-monophosphate hydrolase 1, p36. Engineered: yes
3.01Å     R-factor:   0.185     R-free:   0.268
Authors: K.Wallden,P.Stenmark,C.Arrowsmith,H.Berglund,R.Collins,A.Edw M.Ehn,S.Flodin,A.Flores,S.Graslund,M.Hammarstrom,M.Hallberg B.Holmberg,L.Schiavone,M.Hogbom,T.Kotenyova,A.Magnusdottir, P.Nilsson-Ehle,T.Nyman,D.Ogg,C.Persson,J.Sagemark,M.Sundstr A.G.Thorsell,J.Uppenberg,S.Van Den Berg,J.Weigelt,M.Welin, P.Nordlund
Key ref:
K.Walldén et al. (2007). Crystal structure of human cytosolic 5'-nucleotidase II: insights into allosteric regulation and substrate recognition. J Biol Chem, 282, 17828-17836. PubMed id: 17405878 DOI: 10.1074/jbc.M700917200
09-Feb-07     Release date:   03-Apr-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9H0P0  (5NT3_HUMAN) -  Cytosolic 5'-nucleotidase 3A
336 a.a.
273 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 5'-nucleotidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: A 5'-ribonucleotide + H2O = a ribonucleoside + phosphate
+ H(2)O
= ribonucleoside
Bound ligand (Het Group name = PO4)
corresponds exactly
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biochemical function     magnesium ion binding     2 terms  


DOI no: 10.1074/jbc.M700917200 J Biol Chem 282:17828-17836 (2007)
PubMed id: 17405878  
K.Walldén, P.Stenmark, T.Nyman, S.Flodin, S.Gräslund, P.Loppnau, V.Bianchi, P.Nordlund.
Cytosolic 5'-nucleotidase II catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates and regulates the IMP and GMP pools within the cell. It possesses phosphotransferase activity and thereby also catalyzes the reverse reaction. Both reactions are allosterically activated by adenine-based nucleotides and 2,3-bisphosphoglycerate. We have solved structures of cytosolic 5'-nucleotidase II as native protein (2.2 Angstrom) and in complex with adenosine (1.5 Angstrom) and beryllium trifluoride (2.15 Angstrom) The tetrameric enzyme is structurally similar to enzymes of the haloacid dehalogenase (HAD) superfamily, including mitochondrial 5'(3')-deoxyribonucleotidase and cytosolic 5'-nucleotidase III but possesses additional regulatory regions that contain two allosteric effector sites. At effector site 1 located near a subunit interface we modeled diadenosine tetraphosphate with one adenosine moiety in each subunit. This efficiently glues the tetramer subunits together in pairs. The model shows why diadenosine tetraphosphate but not diadenosine triphosphate activates the enzyme and supports a role for cN-II during apoptosis when the level of diadenosine tetraphosphate increases. We have also modeled 2,3-bisphosphoglycerate in effector site 1 using one phosphate site from each subunit. By comparing the structure of cytosolic 5'-nucleotidase II with that of mitochondrial 5'(3')-deoxyribonucleotidase in complex with dGMP, we identified residues involved in substrate recognition.
  Selected figure(s)  
Figure 5.
FIGURE 5. Effector sites 1 and 2 of cN-II with bound adenosine and sulfate. Omit F[o] - F[c] maps are covering adenosine with level of 4.5 in effector site 1 and level of 3 in effector site 2. A, stereo image of adenosine bound in effector site 1, with adenosine and amino acid residues colored in turquoise. B, stereo image of effector site 1 from two adjacent subunits connected through interface A. Salt bridges are indicated by the dotted lines. Nitrogens are shown in blue, oxygens in red, and sulfur in yellow. C, stereo image of adenosine bound in effector site 2. Note that the ribose moiety is disordered so that the electron density cannot confirm its location. Waters are colored in red. Polar atoms are color-coded as following: nitrogen in blue, oxygens in red, and sulfur in yellow.
Figure 7.
FIGURE 7. Two subunits of the tetrameric cN-II with three positively charged regions (K(25)KYRR), (K(359)SKKRQ), and (Q(420)RRIKK) shown in orange. Adenosines (white), sulfates (yellow and red), and magnesium (yellow) are also shown. Nitrogens are shown in blue and oxygens in red. The C-terminal end of the structure (residue 488) is marked C.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 17828-17836) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23377183 J.A.Meyer, J.Wang, L.E.Hogan, J.J.Yang, S.Dandekar, J.P.Patel, Z.Tang, P.Zumbo, S.Li, J.Zavadil, R.L.Levine, T.Cardozo, S.P.Hunger, E.A.Raetz, W.E.Evans, D.J.Morrison, C.E.Mason, and W.L.Carroll (2013).
Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia.
  Nat Genet, 45, 290-294.  
21396942 K.Walldén, and P.Nordlund (2011).
Structural Basis for the Allosteric Regulation and Substrate Recognition of Human Cytosolic 5'-Nucleotidase II.
  J Mol Biol, 408, 684-696.
PDB codes: 2xcv 2xcw 2xcx 2xjb 2xjc 2xjd 2xje 2xjf
21029378 R.Pesi, S.Allegrini, M.G.Careddu, D.N.Filoni, M.Camici, and M.G.Tozzi (2010).
Active and regulatory sites of cytosolic 5'-nucleotidase.
  FEBS J, 277, 4863-4872.  
19418484 P.Mirandola, G.Gobbi, I.Sponzilli, C.Malinverno, A.Cavazzoni, R.Alfieri, P.G.Petronini, and M.Vitale (2009).
TRAIL-induced apoptosis of FHIT-negative lung cancer cells is inhibited by FHIT re-expression.
  J Cell Physiol, 220, 492-498.  
18282486 J.Weigelt, L.D.McBroom-Cerajewski, M.Schapira, Y.Zhao, C.H.Arrowsmith, and C.H.Arrowmsmith (2008).
Structural genomics and drug discovery: all in the family.
  Curr Opin Chem Biol, 12, 32-39.  
18757419 L.Li, B.Fridley, K.Kalari, G.Jenkins, A.Batzler, S.Safgren, M.Hildebrandt, M.Ames, D.Schaid, and L.Wang (2008).
Gemcitabine and cytosine arabinoside cytotoxicity: association with lymphoblastoid cell expression.
  Cancer Res, 68, 7050-7058.  