PDBsum entry 1e9z

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Hydrolase PDB id
Protein chains
238 a.a. *
569 a.a. *
_NI ×2
Waters ×78
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of helicobacter pylori urease
Structure: Urease subunit alpha. Chain: a. Synonym: urea amidohydrolase subunit alpha. Engineered: yes. Urease subunit beta. Chain: b. Synonym: urea amidohydrolase subunit beta. Engineered: yes
Source: Helicobacter pylori. Organism_taxid: 210. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
Biol. unit: Homo-Dodecamer (from PDB file)
3.00Å     R-factor:   0.212     R-free:   0.284
Authors: N.-C.Ha,S.-T.Oh,B.-H.Oh
Key ref:
N.C.Ha et al. (2001). Supramolecular assembly and acid resistance of Helicobacter pylori urease. Nat Struct Biol, 8, 505-509. PubMed id: 11373617 DOI: 10.1038/88563
01-Nov-00     Release date:   01-Nov-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P14916  (URE23_HELPY) -  Urease subunit alpha
238 a.a.
238 a.a.*
Protein chain
Pfam   ArchSchema ?
P69996  (URE1_HELPY) -  Urease subunit beta
569 a.a.
569 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.  - Urease.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Urea + H2O = CO2 + 2 NH3
+ H(2)O
= CO(2)
+ 2 × NH(3)
      Cofactor: Ni(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     nitrogen compound metabolic process   4 terms 
  Biochemical function     hydrolase activity     4 terms  


    Added reference    
DOI no: 10.1038/88563 Nat Struct Biol 8:505-509 (2001)
PubMed id: 11373617  
Supramolecular assembly and acid resistance of Helicobacter pylori urease.
N.C.Ha, S.T.Oh, J.Y.Sung, K.A.Cha, M.H.Lee, B.H.Oh.
Helicobacter pylori, an etiologic agent in a variety of gastroduodenal diseases, produces a large amount of urease, which is believed to neutralize gastric acid by producing ammonia for the survival of the bacteria. Up to 30% of the enzyme associates with the surface of intact cells upon lysis of neighboring bacteria. The role of the enzyme at the extracellular location has been a subject of controversy because the purified enzyme is irreversibly inactivated below pH 5. We have determined the crystal structure of H. pylori urease, which has a 1.1 MDa spherical assembly of 12 catalytic units with an outer diameter of approximately 160 A. Under physiologically relevant conditions, the activity of the enzyme remains unaffected down to pH 3. Activity assays under different conditions indicated that the cluster of the 12 active sites on the supramolecular assembly may be critical for the survival of the enzyme at low pH. The structure provides a novel example of a molecular assembly adapted for acid resistance that, together with the low Km value of the enzyme, is likely to enable the organism to inhabit the hostile niche.
  Selected figure(s)  
Figure 1.
Figure 1. Structure of H. pylori urease. a, Ribbon diagram of the trimeric unit. One unit is represented with wider ribbons, and the others are differently colored. Each unit consists of the -subunit (blue, residues 1 - 569) and two physically distinct domains of the -subunit, the N-terminal domain (red) and the C-terminal domain (magenta). The segment in yellow represents the unique extension of 27 amino acids ( 212 - 238) that is involved in the formation of the tetramer of the trimeric units as shown in panel (c). b, The dodecameric assembly viewed along the three-fold axis of the trimeric unit. The four trimeric units are in different colors. c, The C traces of the dodecameric assembly are shown in a similar orientation as seen in the electron microscopic image^14 of H. pylori urease in the inset. The scale bars in the main picture and the inset indicate the lengths 100 and 100 nm, respectively. The additional sequence at the C-terminus of the -subunit is displayed as yellow ribbons. A trimer at the back of the figure is omitted for clarity. d, The dodecameric structure viewed perpendicular to the two-fold axis. The hole open to the internal cavity has the dimensions of 22 in width and 10 in height. The circles in panel (b -d) indicate the locations of the active sites, which are distributed evenly on the outer surface of the spherical structure. e, A close-up view of the area in the red rectangle in panel (c). For clarity, the nearby residues interacting with the terminal loop are omitted.
Figure 3.
Figure 3. The flap and the active site of H. pylori urease. a, Superposition of the open (blue) and the closed (magenta) active sites of the enzyme. The opening and closure of the flap, which depends on the binding of AHA to the active site (encircled), are shown. b, A sequence alignment of the flap (helix-turn-helix) and flanking regions in H. pylori (Hp), K. aerogenes (Ka) and B. pasteurii (Bp) ureases. Residues identical in the three ureases are in red. The asterisks indicate the nonconserved residues in H. pylori urease compared to the other ureases. These residues in H. pylori urease are hydrophilic substitutions except for Ala 312. The asterisks are shown in panel (a) in the same colors to indicate the positions of these residues. c, Stereo view of the superposed C traces of H. pylori urease (blue lines) and K. aerogenes urease (red lines; PDB code 1FWE) showing the active sites, both occupied by AHA. The inhibitor and the side chains of the enzyme involved in the chelation of the catalytic bi-nickel center are shown with electron densities. The 2F[o] - F[c] map contoured at 1.0 is in green, and the F[o] - F[c] map contoured at 2.5 is in cyan. The electron density maps were calculated with the omission of AHA and the nickel ions.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 505-509) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21457123 P.Kosikowska, and L.Berlicki (2011).
Urease inhibitors as potential drugs for gastric and urinary tract infections: a patent review.
  Expert Opin Ther Pat, 21, 945-957.  
20960531 G.Zanotti, and L.Cendron (2010).
Functional and structural aspects of Helicobacter pylori acidic stress response factors.
  IUBMB Life, 62, 715-723.  
20442959 H.Kaluarachchi, K.C.Chan Chung, and D.B.Zamble (2010).
Microbial nickel proteins.
  Nat Prod Rep, 27, 681-694.  
20061471 K.Schauer, C.Muller, M.Carrière, A.Labigne, C.Cavazza, and H.De Reuse (2010).
The Helicobacter pylori GroES cochaperonin HspA functions as a specialized nickel chaperone and sequestration protein through its unique C-terminal extension.
  J Bacteriol, 192, 1231-1237.  
20437155 L.Wang, X.F.Liu, S.Yun, X.P.Yuan, X.H.Mao, C.Wu, W.J.Zhang, K.Y.Liu, G.Guo, D.S.Lu, W.D.Tong, A.D.Wen, and Q.M.Zou (2010).
Protection against Helicobacter pylori infection by a trivalent fusion vaccine based on a fragment of urease B-UreB414.
  J Microbiol, 48, 223-228.  
20635345 R.Lam, V.Romanov, K.Johns, K.P.Battaile, J.Wu-Brown, J.L.Guthrie, R.P.Hausinger, E.F.Pai, and N.Y.Chirgadze (2010).
Crystal structure of a truncated urease accessory protein UreF from Helicobacter pylori.
  Proteins, 78, 2839-2848.
PDB code: 3cxn
21124783 T.D.Schoep, A.Fulurija, F.Good, W.Lu, R.P.Himbeck, C.Schwan, S.S.Choi, D.E.Berg, P.R.Mittl, M.Benghezal, and B.J.Marshall (2010).
Surface properties of Helicobacter pylori urease complex are essential for persistence.
  PLoS One, 5, e15042.  
  20046957 E.L.Carter, N.Flugga, J.L.Boer, S.B.Mulrooney, and R.P.Hausinger (2009).
Interplay of metal ions and urease.
  Metallomics, 1, 207-221.  
19476442 M.Bellucci, B.Zambelli, F.Musiani, P.Turano, and S.Ciurli (2009).
Helicobacter pylori UreE, a urease accessory protein: specific Ni(2+)- and Zn(2+)-binding properties and interaction with its cognate UreG.
  Biochem J, 422, 91.  
19920336 S.Khan, A.Karim, and S.Iqbal (2009).
Helicobacter urease: niche construction at the single molecule level.
  J Biosci, 34, 503-511.  
19759826 S.Müller, M.Götz, and D.Beier (2009).
Histidine residue 94 is involved in pH sensing by histidine kinase ArsS of Helicobacte pylori.
  PLoS One, 4, e6930.  
  18607103 A.Balasubramanian, and K.Ponnuraj (2008).
Purification, crystallization and preliminary X-ray analysis of urease from pigeon pea (Cajanus cajan).
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 662-664.  
17991752 E.Hifumi, F.Morihara, K.Hatiuchi, T.Okuda, A.Nishizono, and T.Uda (2008).
Catalytic features and eradication ability of antibody light-chain UA15-L against Helicobacter pylori.
  J Biol Chem, 283, 899-907.  
18306426 F.Morihara, E.Hifumi, M.Yamada, A.Nishizono, and T.Uda (2008).
Therapeutic effects of molecularly designed antigen UREB138 for mice infected with Helicobacter pylori.
  Biotechnol Bioeng, 100, 634-643.  
18564183 J.Stoof, S.Breijer, R.G.Pot, D.van der Neut, E.J.Kuipers, J.G.Kusters, and A.H.van Vliet (2008).
Inverse nickel-responsive regulation of two urease enzymes in the gastric pathogen Helicobacter mustelae.
  Environ Microbiol, 10, 2586-2597.  
18823937 S.Quiroz-Valenzuela, S.C.Sukuru, R.P.Hausinger, L.A.Kuhn, and W.T.Heller (2008).
The structure of urease activation complexes examined by flexibility analysis, mutagenesis, and small-angle X-ray scattering.
  Arch Biochem Biophys, 480, 51-57.  
18443695 W.Z.Lee, H.S.Tseng, M.Y.Ku, and T.S.Kuo (2008).
Dinickel complexes of disubstituted benzoate polydentate ligands: mimics for the active site of urease.
  Dalton Trans, (), 2538-2541.  
17238922 K.Schauer, B.Gouget, M.Carrière, A.Labigne, and Reuse (2007).
Novel nickel transport mechanism across the bacterial outer membrane energized by the TonB/ExbB/ExbD machinery.
  Mol Microbiol, 63, 1054-1068.  
17510959 M.Salomone-Stagni, B.Zambelli, F.Musiani, and S.Ciurli (2007).
A model-based proposal for the role of UreF as a GTPase-activating protein in the urease active site biosynthesis.
  Proteins, 68, 749-761.  
17309745 S.Kabir (2007).
The current status of Helicobacter pylori vaccines: a review.
  Helicobacter, 12, 89.  
17030579 G.S.Davis, E.L.Flannery, and H.L.Mobley (2006).
Helicobacter pylori HP1512 is a nickel-responsive NikR-regulated outer membrane protein.
  Infect Immun, 74, 6811-6820.  
16847081 J.G.Kusters, A.H.van Vliet, and E.J.Kuipers (2006).
Pathogenesis of Helicobacter pylori infection.
  Clin Microbiol Rev, 19, 449-490.  
16937256 L.Zhang, S.B.Mulrooney, A.F.Leung, Y.Zeng, B.B.Ko, R.P.Hausinger, and H.Sun (2006).
Inhibition of urease by bismuth(III): implications for the mechanism of action of bismuth drugs.
  Biometals, 19, 503-511.  
16859909 Z.Amtul, N.Kausar, C.Follmer, R.F.Rozmahel, Atta-Ur-Rahman, S.A.Kazmi, M.S.Shekhani, J.L.Eriksen, K.M.Khan, and M.I.Choudhary (2006).
Cysteine based novel noncompetitive inhibitors of urease(s)--distinctive inhibition susceptibility of microbial and plant ureases.
  Bioorg Med Chem, 14, 6737-6744.  
15542602 B.Zambelli, M.Stola, F.Musiani, K.De Vriendt, B.Samyn, B.Devreese, J.Van Beeumen, P.Turano, A.Dikiy, D.A.Bryant, and S.Ciurli (2005).
UreG, a chaperone in the urease assembly process, is an intrinsically unstructured GTPase that specifically binds Zn2+.
  J Biol Chem, 280, 4684-4695.  
16234936 C.Beddie, C.E.Webster, and M.B.Hall (2005).
Urea decomposition facilitated by a urease model complex: a theoretical investigation.
  Dalton Trans, (), 3542-3551.  
16128818 E.Hifumi, K.Hatiuchi, T.Okuda, A.Nishizono, Y.Okamura, and T.Uda (2005).
Specific degradation of H. pylori urease by a catalytic antibody light chain.
  FEBS J, 272, 4497-4505.  
16181352 G.S.Davis, and H.L.Mobley (2005).
Contribution of dppA to urease activity in Helicobacter pylori 26695.
  Helicobacter, 10, 416-423.  
16199586 J.K.Kim, S.B.Mulrooney, and R.P.Hausinger (2005).
Biosynthesis of active Bacillus subtilis urease in the absence of known urease accessory proteins.
  J Bacteriol, 187, 7150-7154.  
15717330 S.Backert, T.Kwok, M.Schmid, M.Selbach, S.Moese, R.M.Peek, W.König, T.F.Meyer, and P.R.Jungblut (2005).
Subproteomes of soluble and structure-bound Helicobacter pylori proteins analyzed by two-dimensional gel electrophoresis and mass spectrometry.
  Proteomics, 5, 1331-1345.  
15806982 T.Iizumi, S.Yamanishi, Y.Kumagai, K.Nagata, S.Kamiya, K.Hirota, E.Watanabe, C.Sakamoto, and H.Takahashi (2005).
Augmentation of Helicobacter pylori urease activity by its specific IgG antibody: implications for bacterial colonization enhancement.
  Biomed Res, 26, 35-42.  
15488389 A.H.van Vliet, F.D.Ernst, and J.G.Kusters (2004).
NikR-mediated regulation of Helicobacter pylori acid adaptation.
  Trends Microbiol, 12, 489-494.  
15264235 A.J.Heck, and R.H.Van Den Heuvel (2004).
Investigation of intact protein complexes by mass spectrometry.
  Mass Spectrom Rev, 23, 368-389.  
15501814 D.Bumann, H.Habibi, B.Kan, M.Schmid, C.Goosmann, V.Brinkmann, T.F.Meyer, and P.R.Jungblut (2004).
Lack of stage-specific proteins in coccoid Helicobacter pylori cells.
  Infect Immun, 72, 6738-6742.  
14769802 H.S.Won, Y.H.Lee, J.H.Kim, I.S.Shin, M.H.Lee, and B.J.Lee (2004).
Structural characterization of the nickel-binding properties of Bacillus pasteurii urease accessory protein (Ure)E in solution.
  J Biol Chem, 279, 17466-17472.  
15162449 R.Fujii, F.Morihara, K.Fukushima, T.Oku, E.Hifumi, and T.Uda (2004).
Recombinant antigen from Helicobacter pylori urease as vaccine against H. pylori-associated disease.
  Biotechnol Bioeng, 86, 737-746.  
15112296 R.Fujii, F.Morihara, T.Oku, E.Hifumi, and T.Uda (2004).
Epitope mapping and features of the epitope for monoclonal antibodies inhibiting enzymatic activity of Helicobacter pylori urease.
  Biotechnol Bioeng, 86, 434-444.  
14981304 T.Mizuki, M.Kamekura, S.DasSarma, T.Fukushima, R.Usami, Y.Yoshida, and K.Horikoshi (2004).
Ureases of extreme halophiles of the genus Haloarcula with a unique structure of gene cluster.
  Biosci Biotechnol Biochem, 68, 397-406.  
14749331 Z.Chang, J.Kuchar, and R.P.Hausinger (2004).
Chemical cross-linking and mass spectrometric identification of sites of interaction for UreD, UreF, and urease.
  J Biol Chem, 279, 15305-15313.  
12471160 G.Sachs, D.L.Weeks, K.Melchers, and D.R.Scott (2003).
The gastric biology of Helicobacter pylori.
  Annu Rev Physiol, 65, 349-369.  
12829270 S.B.Mulrooney, and R.P.Hausinger (2003).
Nickel uptake and utilization by microorganisms.
  FEMS Microbiol Rev, 27, 239-261.  
12003947 K.Stingl, E.M.Uhlemann, R.Schmid, K.Altendorf, and E.P.Bakker (2002).
Energetics of Helicobacter pylori and its implications for the mechanism of urease-dependent acid tolerance at pH 1.
  J Bacteriol, 184, 3053-3060.  
11827807 K.Stingl, K.Altendorf, and E.P.Bakker (2002).
Acid survival of Helicobacter pylori: how does urease activity trigger cytoplasmic pH homeostasis?
  Trends Microbiol, 10, 70-74.  
12183559 P.Londoño-Arcila, D.Freeman, H.Kleanthous, A.M.O'Dowd, S.Lewis, A.K.Turner, E.L.Rees, T.J.Tibbitts, J.Greenwood, T.P.Monath, and M.J.Darsley (2002).
Attenuated Salmonella enterica serovar Typhi expressing urease effectively immunizes mice against Helicobacter pylori challenge as part of a heterologous mucosal priming-parenteral boosting vaccination regimen.
  Infect Immun, 70, 5096-5106.  
11500473 C.S.Beckwith, D.J.McGee, H.L.Mobley, and L.K.Riley (2001).
Cloning, expression, and catalytic activity of Helicobacter hepaticus urease.
  Infect Immun, 69, 5914-5920.  
11825711 G.Sachs, D.Scott, D.Weeks, and K.Melchers (2001).
The importance of the surface urease of Helicobacter pylori: fact or fiction?
  Trends Microbiol, 9, 532-534.  
11598027 K.Hirota, K.Nagata, Y.Norose, S.Futagami, Y.Nakagawa, H.Senpuku, M.Kobayashi, and H.Takahashi (2001).
Identification of an antigenic epitope in Helicobacter pylori urease that induces neutralizing antibody production.
  Infect Immun, 69, 6597-6603.  
11737644 S.Bury-Moné, S.Skouloubris, A.Labigne, and H.De Reuse (2001).
The Helicobacter pylori UreI protein: role in adaptation to acidity and identification of residues essential for its activity and for acid activation.
  Mol Microbiol, 42, 1021-1034.  
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.