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PDBsum entry 1mas

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protein metals Protein-protein interface(s) links
Hydrolase PDB id
1mas
Jmol
Contents
Protein chains
308 a.a. *
Metals
__K ×2
Waters ×73
* Residue conservation analysis
PDB id:
1mas
Name: Hydrolase
Title: Purine nucleoside hydrolase
Structure: Inosine-uridine nucleoside n-ribohydrolase. Chain: a, b. Synonym: purine nucleoside hydrolase, inosine-uridine nucleosidase, iu-nh. Engineered: yes. Mutation: yes
Source: Crithidia fasciculata. Organism_taxid: 5656. Gene: iu-nh from c.Fasciculata. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
2.50Å     R-factor:   0.170    
Authors: M.Degano,D.N.Gopaul,G.Scapin,V.L.Schramm,J.C.Sacchettini
Key ref:
M.Degano et al. (1996). Three-dimensional structure of the inosine-uridine nucleoside N-ribohydrolase from Crithidia fasciculata. Biochemistry, 35, 5971-5981. PubMed id: 8634238 DOI: 10.1021/bi952999m
Date:
18-Dec-95     Release date:   17-Aug-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q27546  (IUNH_CRIFA) -  Inosine-uridine preferring nucleoside hydrolase
Seq:
Struc:
315 a.a.
308 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   2 terms 
  Biochemical function     hydrolase activity     4 terms  

 

 
DOI no: 10.1021/bi952999m Biochemistry 35:5971-5981 (1996)
PubMed id: 8634238  
 
 
Three-dimensional structure of the inosine-uridine nucleoside N-ribohydrolase from Crithidia fasciculata.
M.Degano, D.N.Gopaul, G.Scapin, V.L.Schramm, J.C.Sacchettini.
 
  ABSTRACT  
 
Protozoan parasites rely on the host for purines since they lack a de novo synthetic pathway. Crithidia fasciculata salvages exogenous inosine primarily through hydrolysis of the N-ribosidic bond using several nucleoside hydrolases. The most abundant nucleoside hydrolase is relatively nonspecific but prefers inosine and uridine as substrates. Here we report the three-dimensional structure of the inosine-uridine nucleoside hydrolase (IU-NH) from C. fasciculata determined by X-ray crystallography at a nominal resolution of 2.5 A. The enzyme has an open (alpha, beta) structure which differs from the classical dinucleotide binding fold. IU-nucleoside hydrolase is composed of a mixed eight-stranded beta sheet surrounded by six alpha helices and a small C-terminal lobe composed of four alpha helices. Two short antiparallel beta strands are involved in intermolecular contacts. The catalytic pocket is located at the C-terminal end of beta strands beta 1 and beta 4. Four aspartate residues are located at the bottom of the cavity in a geometry which suggests interaction with the ribose moiety of the nucleoside. These groups could provide the catalytically important interactions to the ribosyl hydroxyls and the stabilizing anion for the oxycarbonium-like transition state. Histidine 241, located on the side of the active site cavity, is the proposed proton donor which facilitates purine base departure [Gopaul, D. N., Meyer, S. L., Degano, M., Sacchettini, J. C., & Schramm, V. L. (1996) Biochemistry 35, 5963-5970]. The substrate binding site is unlike that from purine nucleoside phosphorylase, phosphoribosyltransferases, or uracil DNA glycosylase and thus represents a novel architecture for general acid-base catalysis. This detailed knowledge of the architecture of the active site, together with the previous transition state analysis [Horenstein, B. A., Parkin, D. W., Estupiñán, B., & Schramm, V. L. (1991) Biochemistry 30, 10788-10795], allows analysis of the interactions leading to catalysis and an explanation for the tight-binding inhibitors of the enzyme [Schramm, V. L., Horenstein, B. A., & Kline, P. C. (1994) J. Biol. Chem. 269, 18259-18262].
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21235647 B.Jung, C.Hoffmann, and T.Möhlmann (2011).
Arabidopsis nucleoside hydrolases involved in intracellular and extracellular degradation of purines.
  Plant J, 65, 703-711.  
20529317 G.Garau, L.Muzzolini, P.Tornaghi, and M.Degano (2010).
Active site plasticity revealed from the structure of the enterobacterial N-ribohydrolase RihA bound to a competitive inhibitor.
  BMC Struct Biol, 10, 14.  
18519562 A.Vandemeulebroucke, S.De Vos, E.Van Holsbeke, J.Steyaert, and W.Versées (2008).
A flexible loop as a functional element in the catalytic mechanism of nucleoside hydrolase from trypanosoma vivax.
  J Biol Chem, 283, 22272-22282.
PDB code: 3b9g
18355316 M.Porcelli, L.Concilio, I.Peluso, A.Marabotti, A.Facchiano, and G.Cacciapuoti (2008).
Pyrimidine-specific ribonucleoside hydrolase from the archaeon Sulfolobus solfataricus--biochemical characterization and homology modeling.
  FEBS J, 275, 1900-1914.  
17482543 P.Belenky, F.G.Racette, K.L.Bogan, J.M.McClure, J.S.Smith, and C.Brenner (2007).
Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+.
  Cell, 129, 473-484.  
16714288 M.Marino, M.Deuss, D.I.Svergun, P.V.Konarev, R.Sterner, and O.Mayans (2006).
Structural and mutational analysis of substrate complexation by anthranilate phosphoribosyltransferase from Sulfolobus solfataricus.
  J Biol Chem, 281, 21410-21421.
PDB codes: 1zxy 1zyk 2gvq
14993681 B.Giabbai, and M.Degano (2004).
Cloning, purification, crystallization and X-ray analysis of the Escherichia coli pyrimidine nucleoside hydrolase YeiK.
  Acta Crystallogr D Biol Crystallogr, 60, 524-527.  
15130467 B.Giabbai, and M.Degano (2004).
Crystal structure to 1.7 a of the Escherichia coli pyrimidine nucleoside hydrolase YeiK, a novel candidate for cancer gene therapy.
  Structure, 12, 739-749.
PDB code: 1q8f
15545602 J.A.Roden, B.Belt, J.B.Ross, T.Tachibana, J.Vargas, and M.B.Mudgett (2004).
A genetic screen to isolate type III effectors translocated into pepper cells during Xanthomonas infection.
  Proc Natl Acad Sci U S A, 101, 16624-16629.  
14675552 W.Versées, and J.Steyaert (2003).
Catalysis by nucleoside hydrolases.
  Curr Opin Struct Biol, 13, 731-738.  
11134941 J.E.Lee, K.A.Cornell, M.K.Riscoe, and P.L.Howell (2001).
Expression, purification, crystallization and preliminary X-ray analysis of Escherichia coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase.
  Acta Crystallogr D Biol Crystallogr, 57, 150-152.  
11282633 J.Ogawa, S.Takeda, S.X.Xie, H.Hatanaka, T.Ashikari, T.Amachi, and S.Shimizu (2001).
Purification, characterization, and gene cloning of purine nucleosidase from Ochrobactrum anthropi.
  Appl Environ Microbiol, 67, 1783-1787.  
10737925 Y.J.Gu, and Z.X.Xia (2000).
Crystal structures of the complexes of trichosanthin with four substrate analogs and catalytic mechanism of RNA N-glycosidase.
  Proteins, 39, 37-46.
PDB code: 1qd2
10090282 G.Xiao, M.Tordova, J.Jagadeesh, A.C.Drohat, J.T.Stivers, and G.L.Gilliland (1999).
Crystal structure of Escherichia coli uracil DNA glycosylase and its complexes with uracil and glycerol: structure and glycosylase mechanism revisited.
  Proteins, 35, 13-24.
PDB codes: 1eug 2eug 3eug 5eug
10409664 W.Shi, V.L.Schramm, and S.C.Almo (1999).
Nucleoside hydrolase from Leishmania major. Cloning, expression, catalytic properties, transition state inhibitors, and the 2.5-å crystal structure.
  J Biol Chem, 274, 21114-21120.
PDB code: 1ezr
9586999 M.A.Turner, C.S.Yuan, R.T.Borchardt, M.S.Hershfield, G.D.Smith, and P.L.Howell (1998).
Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength.
  Nat Struct Biol, 5, 369-376.
PDB code: 1a7a
9572842 M.Degano, S.C.Almo, J.C.Sacchettini, and V.L.Schramm (1998).
Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor.
  Biochemistry, 37, 6277-6285.
PDB code: 2mas
9442052 R.Pellé, V.L.Schramm, and D.W.Parkin (1998).
Molecular cloning and expression of a purine-specific N-ribohydrolase from Trypanosoma brucei brucei. Sequence, expression, and molecular analysis.
  J Biol Chem, 273, 2118-2126.  
9521733 Y.Xu, and C.Grubmeyer (1998).
Catalysis in human hypoxanthine-guanine phosphoribosyltransferase: Asp 137 acts as a general acid/base.
  Biochemistry, 37, 4114-4124.  
9132003 D.W.Parkin, G.Limberg, P.C.Tyler, R.H.Furneaux, X.Y.Chen, and V.L.Schramm (1997).
Isozyme-specific transition state inhibitors for the trypanosomal nucleoside hydrolases.
  Biochemistry, 36, 3528-3534.  
9667869 V.L.Schramm (1997).
Enzymatic N-riboside scission in RNA and RNA precursors.
  Curr Opin Chem Biol, 1, 323-331.  
8634237 D.N.Gopaul, S.L.Meyer, M.Degano, J.C.Sacchettini, and V.L.Schramm (1996).
Inosine-uridine nucleoside hydrolase from Crithidia fasciculata. Genetic characterization, crystallization, and identification of histidine 241 as a catalytic site residue.
  Biochemistry, 35, 5963-5970.  
8634245 H.Deng, A.W.Chan, C.K.Bagdassarian, B.Estupiñán, B.Ganem, R.H.Callender, and V.L.Schramm (1996).
Trypanosomal nucleoside hydrolase. Resonance Raman spectroscopy of a transition-state inhibitor complex.
  Biochemistry, 35, 6037-6047.  
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 code is shown on the right.