DB code: M00225

CATH domain 2.30.40.10 : Urease, subunit C; domain 1
3.20.20.140 : TIM Barrel Catalytic domain
2.10.150.10 : Urease, subunit B
3.30.280.10 : Urease; subunit A
E.C. 3.5.1.5
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.30.40.10 : Urease, subunit C; domain 1 D00673 D00675 D00801 D00873 M00030 M00226
3.20.20.140 : TIM Barrel S00231 S00232 M00186 D00673 D00675 D00801 D00873 M00030 M00226
3.30.280.10 : Urease; subunit A M00030 M00226
2.10.150.10 : Urease, subunit B M00030 M00226

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P69996 Urease subunit beta
EC 3.5.1.5
Urea amidohydrolase subunit beta
NP_206872.1 (Protein)
NC_000915.1 (DNA/RNA sequence)
YP_006933994.1 (Protein)
NC_018939.1 (DNA/RNA sequence)
M38.982 (Metallo)
PF01979 (Amidohydro_1)
PF00449 (Urease_alpha)
[Graphical View]
D3UJ80
None YP_003517278.1 (Protein)
NC_013949.1 (DNA/RNA sequence)
M38.982 (Metallo)
PF01979 (Amidohydro_1)
PF00449 (Urease_alpha)
[Graphical View]
P14916 Urease subunit alpha
EC 3.5.1.5
Urea amidohydrolase subunit alpha
NP_206873.1 (Protein)
NC_000915.1 (DNA/RNA sequence)
YP_006933995.1 (Protein)
NC_018939.1 (DNA/RNA sequence)
PF00699 (Urease_beta)
PF00547 (Urease_gamma)
[Graphical View]
D3UJ81
None YP_003517279.1 (Protein)
NC_013949.1 (DNA/RNA sequence)
PF00699 (Urease_beta)
PF00547 (Urease_gamma)
[Graphical View]

KEGG enzyme name
Urease
Urea amidohydrolase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P69996 URE2_HELPY Urea + H(2)O = CO(2) + 2 NH(3). Heterohexamer of 3 UreA (alpha) and 3 UreB (beta) subunits. Four heterohexamers assemble to form a 16 nm dodecameric complex. Cytoplasm. Note=Also associates with the outer membrane upon autolysis of neighboring bacteria. Binds 2 nickel ions per subunit.
D3UJ80 D3UJ80_HELM1 Urea + H(2)O = CO(2) + 2 NH(3). Heterohexamer of 3 UreA (alpha) and 3 UreB (beta) subunits (By similarity). Cytoplasm (By similarity). Binds 2 nickel ions per subunit (By similarity).
P14916 URE23_HELPY Urea + H(2)O = CO(2) + 2 NH(3). Heterohexamer of 3 UreA (alpha) and 3 UreB (beta) subunits. Four heterohexamers assemble to form a 16 nm dodecameric complex. Cytoplasm. Note=Also associates with the outer membrane upon autolysis of neighboring bacteria.
D3UJ81 D3UJ81_HELM1 Urea + H(2)O = CO(2) + 2 NH(3).

KEGG Pathways
Map code Pathways E.C.
MAP00220 Urea cycle and metabolism of amino groups
MAP00230 Purine metabolism
MAP00791 Atrazine degradation

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00291 C00086 C00001 C00011 C00014 I00127 C01563
E.C.
Compound Nickel Urea H2O CO2 NH3 Diaminohydroxymethanolate Carbamate
Type heavy metal amide group,amine group H2O others amine group,organic ion
ChEBI 28112
28112
16199
48376
16199
48376
15377
15377
16526
16526
16134
16134
PubChem 935
935
1176
1176
22247451
962
22247451
962
280
280
222
222
1e9yB01 Unbound Unbound Unbound Unbound Unbound Unbound
1e9zB01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaC01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaF01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaI01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaL01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaO01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaR01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkC01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkF01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkI01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkL01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkO01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkR01 Unbound Unbound Unbound Unbound Unbound Unbound
1e9yB02 Bound:2x_NI Unbound Unbound Unbound Unbound Intermediate-analogue:HAE
1e9zB02 Bound:2x_NI Unbound Unbound Unbound Unbound Unbound
3qgaC02 Analogue:2x_FE Unbound Unbound Unbound Unbound Unbound
3qgaF02 Analogue:2x_FE Unbound Unbound Unbound Unbound Unbound
3qgaI02 Analogue:2x_FE Unbound Unbound Unbound Unbound Unbound
3qgaL02 Analogue:2x_FE Unbound Unbound Unbound Unbound Unbound
3qgaO02 Analogue:2x_FE Unbound Unbound Unbound Unbound Unbound
3qgaR02 Analogue:2x_FE Unbound Unbound Unbound Unbound Unbound
3qgkC02 Analogue:2x_FE Unbound Unbound Unbound Unbound Unbound
3qgkF02 Analogue:2x_FE Unbound Unbound Unbound Unbound Unbound
3qgkI02 Analogue:2x_FE Unbound Unbound Unbound Unbound Unbound
3qgkL02 Analogue:2x_FE Unbound Unbound Unbound Unbound Unbound
3qgkO02 Analogue:2x_FE Unbound Unbound Unbound Unbound Unbound
3qgkR02 Analogue:2x_FE Unbound Unbound Unbound Unbound Unbound
1e9yA01 Unbound Unbound Unbound Unbound Unbound Unbound
1e9zA01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaA02 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaD02 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaG02 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaJ02 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaM02 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaP02 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkA02 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkD02 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkG02 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkJ02 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkM02 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkP02 Unbound Unbound Unbound Unbound Unbound Unbound
1e9yA02 Unbound Unbound Unbound Unbound Unbound Unbound
1e9zA02 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaA01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaD01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaG01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaJ01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaM01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgaP01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkA01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkD01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkG01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkJ01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkM01 Unbound Unbound Unbound Unbound Unbound Unbound
3qgkP01 Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P18314, P41020, P69996 & literature [17], [22], [31]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1e9yB01
1e9zB01
3qgaC01
3qgaF01
3qgaI01
3qgaL01
3qgaO01
3qgaR01
3qgkC01
3qgkF01
3qgkI01
3qgkL01
3qgkO01
3qgkR01
1e9yB02 HIS 221;ASP 223;HIS 322;ARG 338 KCX 219(Nickel-1 & -2);HIS 248;HIS 274(Nickel-1);HIS 136;HIS 138;ASP 362(Nickel-2) KCX 219(Carbamylated LYS)
1e9zB02 HIS 221;ASP 223;HIS 322;ARG 338 KCX 219(Nickel-1 & -2);HIS 248;HIS 274(Nickel-1);HIS 136;HIS 138;ASP 362(Nickel-2) KCX 219(Carbamylated LYS)
3qgaC02 HIS 220;ASP 222;HIS 321;ARG 337 KCX 218(Nickel-1 & -2);HIS 247;HIS 273(Nickel-1);HIS 135;HIS 137;ASP 361(Nickel-2) KCX 218(Carbamylated LYS) invisible 329-332
3qgaF02 HIS 220;ASP 222;HIS 321;ARG 337 KCX 218(Nickel-1 & -2);HIS 247;HIS 273(Nickel-1);HIS 135;HIS 137;ASP 361(Nickel-2) KCX 218(Carbamylated LYS) invisible 329-332
3qgaI02 HIS 220;ASP 222;HIS 321;ARG 337 KCX 218(Nickel-1 & -2);HIS 247;HIS 273(Nickel-1);HIS 135;HIS 137;ASP 361(Nickel-2) KCX 218(Carbamylated LYS) invisible 329-332
3qgaL02 HIS 220;ASP 222;HIS 321;ARG 337 KCX 218(Nickel-1 & -2);HIS 247;HIS 273(Nickel-1);HIS 135;HIS 137;ASP 361(Nickel-2) KCX 218(Carbamylated LYS) invisible 329-332
3qgaO02 HIS 220;ASP 222;HIS 321;ARG 337 KCX 218(Nickel-1 & -2);HIS 247;HIS 273(Nickel-1);HIS 135;HIS 137;ASP 361(Nickel-2) KCX 218(Carbamylated LYS) invisible 329-332
3qgaR02 HIS 220;ASP 222;HIS 321;ARG 337 KCX 218(Nickel-1 & -2);HIS 247;HIS 273(Nickel-1);HIS 135;HIS 137;ASP 361(Nickel-2) KCX 218(Carbamylated LYS) invisible 329-332
3qgkC02 HIS 220;ASP 222;HIS 321;ARG 337 KCX 218(Nickel-1 & -2);HIS 247;HIS 273(Nickel-1);HIS 135;HIS 137;ASP 361(Nickel-2) KCX 218(Carbamylated LYS) invisible 329-332
3qgkF02 HIS 220;ASP 222;HIS 321;ARG 337 KCX 218(Nickel-1 & -2);HIS 247;HIS 273(Nickel-1);HIS 135;HIS 137;ASP 361(Nickel-2) KCX 218(Carbamylated LYS) invisible 329-332
3qgkI02 HIS 220;ASP 222;HIS 321;ARG 337 KCX 218(Nickel-1 & -2);HIS 247;HIS 273(Nickel-1);HIS 135;HIS 137;ASP 361(Nickel-2) KCX 218(Carbamylated LYS) invisible 329-332
3qgkL02 HIS 220;ASP 222;HIS 321;ARG 337 KCX 218(Nickel-1 & -2);HIS 247;HIS 273(Nickel-1);HIS 135;HIS 137;ASP 361(Nickel-2) KCX 218(Carbamylated LYS) invisible 329-332
3qgkO02 HIS 220;ASP 222;HIS 321;ARG 337 KCX 218(Nickel-1 & -2);HIS 247;HIS 273(Nickel-1);HIS 135;HIS 137;ASP 361(Nickel-2) KCX 218(Carbamylated LYS) invisible 329-332
3qgkR02 HIS 220;ASP 222;HIS 321;ARG 337 KCX 218(Nickel-1 & -2);HIS 247;HIS 273(Nickel-1);HIS 135;HIS 137;ASP 361(Nickel-2) KCX 218(Carbamylated LYS) invisible 329-332
1e9yA01
1e9zA01
3qgaA02
3qgaD02
3qgaG02
3qgaJ02
3qgaM02
3qgaP02
3qgkA02
3qgkD02
3qgkG02
3qgkJ02
3qgkM02
3qgkP02
1e9yA02
1e9zA02
3qgaA01
3qgaD01
3qgaG01
3qgaJ01
3qgaM01
3qgaP01
3qgkA01
3qgkD01
3qgkG01
3qgkJ01
3qgkM01
3qgkP01

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[7]
figure, p.996
[12]
Figure 2, Figure 6, p.333-337
[17]
Figure 8, p.211-213
[19]
Figure 7, p.5394-5395
[20]
FIGURE 1, FIGURE 8, p.8583-8584
[22]
Figure 2, Figure 3, Figure 4, p.796
[23]
[24]
Fig.6, p.787
[31]
Figure 3, Figure 7, Figure 8, Figure 10, p.15335-15337
[34]
Figure 13, p.6943
[35]
Figure 4, Figure 11, p.11842
[36]
Figure 4, Figure 5, Figure 6, Figure 13, Figure 16, Figure 18
[37]
Figure 1, Figure 2, Figure 3
[40]
Scheme 2, p.521

References
[1]
Resource
Comments
Medline ID
PubMed ID 1400317
Journal J Biol Chem
Year 1992
Volume 267
Pages 20024-7
Authors Martin PR, Hausinger RP
Title Site-directed mutagenesis of the active site cysteine in Klebsiella aerogenes urease.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 1404395
Journal J Mol Biol
Year 1992
Volume 227
Pages 934-7
Authors Jabri E, Lee MH, Hausinger RP, Karplus PA
Title Preliminary crystallographic studies of urease from jack bean and from Klebsiella aerogenes.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8318888
Journal Protein Sci
Year 1993
Volume 2
Pages 1034-41
Authors Park IS, Hausinger RP
Title Site-directed mutagenesis of Klebsiella aerogenes urease: identification of histidine residues that appear to function in nickel ligation, substrate binding, and catalysis.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 7565414
Journal Microbiol Rev
Year 1995
Volume 59
Pages 451-80
Authors Mobley HL, Island MD, Hausinger RP
Title Molecular biology of microbial ureases.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8535259
Journal Protein Sci
Year 1995
Volume 4
Pages 2234-6
Authors Moncrief MB, Hom LG, Jabri E, Karplus PA, Hausinger RP
Title Urease activity in the crystalline state.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID 95273988
PubMed ID 7754395
Journal Science
Year 1995
Volume 268
Pages 998-1004
Authors Jabri E, Carr MB, Hausinger RP, Karplus PA
Title The crystal structure of urease from Klebsiella aerogenes.
Related PDB 1kau 2kau 3kau
Related UniProtKB P18314 P18315 P18316
[7]
Resource
Comments
Medline ID
PubMed ID 7754394
Journal Science
Year 1995
Volume 268
Pages 996-7
Authors Lippard SJ
Title At last--the crystal structure of urease.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID 96346054
PubMed ID 8718850
Journal Biochemistry
Year 1996
Volume 35
Pages 10616-26
Authors Jabri E, Karplus PA
Title Structures of the Klebsiella aerogenes urease apoenzyme and two active-site mutants.
Related PDB 1kra 1krb 1krc
Related UniProtKB P18314 P18315 P18316
[9]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 8702515
Journal J Biol Chem
Year 1996
Volume 271
Pages 18632-7
Authors Park IS, Michel LO, Pearson MA, Jabri E, Karplus PA, Wang S, Dong J, Scott RA, Koehler BP, Johnson MK, Hausinger RP
Title Characterization of the mononickel metallocenter in H134A mutant urease.
Related PDB 1fwi
Related UniProtKB
[10]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9201965
Journal Biochemistry
Year 1997
Volume 36
Pages 8164-72
Authors Pearson MA, Michel LO, Hausinger RP, Karplus PA
Title Structures of Cys319 variants and acetohydroxamate-inhibited Klebsiella aerogenes urease.
Related PDB 1fwa 1fwb 1fwc 1fwd 1fwe 1fwf 1fwg 1fwh 1fwj
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 9144792
Journal Proteins
Year 1997
Volume 28
Pages 72-82
Authors Holm L, Sander C
Title An evolutionary treasure: unification of a broad set of amidohydrolases related to urease.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID
Journal Acc Chem Res
Year 1997
Volume 30
Pages 330?7
Authors Karplus PA, Pearson MA, Hausinger RP
Title 70 Years of Crystalline Urease:? What Have We Learned?
Related PDB
Related UniProtKB
[13]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS).
Medline ID
PubMed ID 9761912
Journal Acta Crystallogr D Biol Crystallogr
Year 1998
Volume 54
Pages 409-12
Authors Benini S, Ciurli S, Rypniewski WR, Wilson KS, Mangani S
Title Crystallization and preliminary high-resolution X-ray diffraction analysis of native and beta-mercaptoethanol-inhibited urease from Bacillus pasteurii.
Related PDB
Related UniProtKB P41020 P41021 P41022
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID 98226663
PubMed ID 9558361
Journal Biochemistry
Year 1998
Volume 37
Pages 6214-20
Authors Pearson MA, Schaller RA, Michel LO, Karplus PA, Hausinger RP
Title Chemical rescue of Klebsiella aerogenes urease variants lacking the carbamylated-lysine nickel ligand.
Related PDB 1a5k 1a5l 1a5m 1a5n 1a5o
Related UniProtKB P18314 P18315 P18316
[15]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID
Journal J Biol Inorg Chem
Year 1998
Volume 3
Pages 268-73
Authors Benini S, Rypniewski WR, Wilson KS, Ciurli S, Mangani S
Title The complex of Bacillus pasteurii urease with beta-mercaptoethanol from X-ray data at 1.65-angstrom resolution.
Related PDB 1ubp
Related UniProtKB
[16]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID
PubMed ID 10555581
Journal J Biol Inorg Chem
Year 1999
Volume 4
Pages 468-77
Authors Yamaguchi K, Cosper NJ, Stalhandske C, Scott RA, Pearson MA, Karplus PA, Hausinger RP
Title Characterization of metal-substituted Klebsiella aerogenes urease.
Related PDB 1ef2
Related UniProtKB P18314 P18315 P18316
[17]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
Medline ID 99148127
PubMed ID 10368287
Journal Structure Fold Des
Year 1999
Volume 7
Pages 205-16
Authors Benini S, Rypniewski WR, Wilson KS, Miletti S, Ciurli S, Mangani S
Title A new proposal for urease mechanism based on the crystal structures of the native and inhibited enzyme from Bacillus pasteurii: why urea hydrolysis costs two nickels.
Related PDB 2ubp 3ubp
Related UniProtKB P41020 P41021 P41022
[18]
Resource
Comments
Medline ID
PubMed ID 11996109
Journal Acta Biochim Pol
Year 2000
Volume 47
Pages 1189-95
Authors Sirko A, Brodzik R
Title Plant ureases: roles and regulation.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 10820010
Journal Biochemistry
Year 2000
Volume 39
Pages 5389-96
Authors Todd MJ, Hausinger RP
Title Fluoride inhibition of Klebsiella aerogenes urease: mechanistic implications of a pseudo-uncompetitive, slow-binding inhibitor.
Related PDB
Related UniProtKB
[20]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), AND MUTAGENESIS OF HIS-219; ASP-221; HIS-320 AND ARG-336.
Medline ID
PubMed ID 10913264
Journal Biochemistry
Year 2000
Volume 39
Pages 8575-84
Authors Pearson MA, Park IS, Schaller RA, Michel LO, Karplus PA, Hausinger RP
Title Kinetic and structural characterization of urease active site variants.
Related PDB 1ejr 1ejs 1ejt 1eju 1ejv
Related UniProtKB P18314 P18315 P18316
[21]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10766443
Journal J Biol Inorg Chem
Year 2000
Volume 5
Pages 110-8
Authors Benini S, Rypniewski WR, Wilson KS, Miletti S, Ciurli S, Mangani S
Title The complex of Bacillus pasteurii urease with acetohydroxamate anion from X-ray data at 1.55 A resolution.
Related PDB 4ubp
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 10798524
Journal J Biomol Struct Dyn
Year 2000
Volume 17
Pages 787-97
Authors Zimmer M
Title Molecular mechanics evaluation of the proposed mechanisms for the degradation of urea by urease.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID
Journal J Am Chem Soc
Year 2000
Volume 122
Pages 9172-77
Authors Barrios AM, Lippard SJ
Title Interaction of Urea with a Hydroxide-Bridged Dinuclear Nickel Center:? An Alternative Model for the Mechanism of Urease.
Related PDB
Related UniProtKB
[24]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11713685
Journal J Biol Inorg Chem
Year 2001
Volume 6
Pages 778-90
Authors Benini S, Rypniewski WR, Wilson KS, Ciurli S, Mangani S
Title Structure-based rationalization of urease inhibition by phosphate: novel insights into the enzyme mechanism.
Related PDB 1ie7
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 11315566
Journal J Biol Inorg Chem
Year 2001
Volume 6
Pages 300-14
Authors Musiani F, Arnofi E, Casadio R, Ciurli S
Title Structure-based computational study of the catalytic and inhibition mechanisms of urease.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 11373609
Journal Nat Struct Biol
Year 2001
Volume 8
Pages 480-2
Authors Dunn BE, Grutter MG
Title Helicobacter pylori springs another surprise.
Related PDB
Related UniProtKB
[27]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS), AND SUBUNIT STRUCTURE.
Medline ID
PubMed ID 11373617
Journal Nat Struct Biol
Year 2001
Volume 8
Pages 505-9
Authors Ha NC, Oh ST, Sung JY, Cha KA, Lee MH, Oh BH
Title Supramolecular assembly and acid resistance of Helicobacter pylori urease.
Related PDB 1e9y 1e9z
Related UniProtKB P14916 P69996
[28]
Resource
Comments
Medline ID
PubMed ID 11300826
Journal Inorg Chem
Year 2001
Volume 40
Pages 1250-5
Authors Barrios AM, Lippard SJ
Title Decomposition of alkyl-substituted urea molecules at a hydroxide-bridged dinickel center.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 11807281
Journal Acta Crystallogr D Biol Crystallogr
Year 2002
Volume 58
Pages 374-6
Authors Sheridan L, Wilmot CM, Cromie KD, van der Logt P, Phillips SE
Title Crystallization and preliminary X-ray structure determination of jack bean urease with a bound antibody fragment.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 12121941
Journal Antimicrob Agents Chemother
Year 2002
Volume 46
Pages 2613-8
Authors Mishra H, Parrill AL, Williamson JS
Title Three-dimensional quantitative structure-activity relationship and comparative molecular field analysis of dipeptide hydroxamic acid Helicobacter pylori urease inhibitors.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 14664576
Journal J Am Chem Soc
Year 2003
Volume 125
Pages 15324-37
Authors Suarez D, Diaz N, Merz KM Jr
Title Ureases: quantum chemical calculations on cluster models.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 12913138
Journal Plant Physiol
Year 2003
Volume 132
Pages 1801-10
Authors Goldraij A, Beamer LJ, Polacco JC
Title Interallelic complementation at the ubiquitous urease coding locus of soybean.
Related PDB
Related UniProtKB
[33]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15038715
Journal J Am Chem Soc
Year 2004
Volume 126
Pages 3714-5
Authors Benini S, Rypniewski WR, Wilson KS, Mangani S, Ciurli S
Title Molecular details of urease inhibition by boric acid: insights into the catalytic mechanism.
Related PDB 1s3t
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 15174863
Journal J Am Chem Soc
Year 2004
Volume 126
Pages 6932-44
Authors Estiu G, Merz KM Jr
Title The hydrolysis of urea and the proficiency of urease.
Related PDB
Related UniProtKB
[35]
Resource
Comments
Medline ID
PubMed ID 15382918
Journal J Am Chem Soc
Year 2004
Volume 126
Pages 11832-42
Authors Estiu G, Merz KM Jr
Title Enzymatic catalysis of urea decomposition: elimination or hydrolysis?
Related PDB
Related UniProtKB
[36]
Resource
Comments
Medline ID
PubMed ID 16584179
Journal Biochemistry
Year 2006
Volume 45
Pages 4429-43
Authors Estiu G, Merz KM Jr
Title Catalyzed decomposition of urea. Molecular dynamics simulations of the binding of urea to urease.
Related PDB
Related UniProtKB
[37]
Resource
Comments
Medline ID
PubMed ID 17676790
Journal J Phys Chem B
Year 2007
Volume 111
Pages 10263-74
Authors Estiu G, Merz KM Jr
Title Competitive hydrolytic and elimination mechanisms in the urease catalyzed decomposition of urea.
Related PDB
Related UniProtKB
[38]
Resource
Comments
Medline ID
PubMed ID 20471401
Journal J Mol Biol
Year 2010
Volume 400
Pages 274-83
Authors Balasubramanian A, Ponnuraj K
Title Crystal structure of the first plant urease from jack bean: 83 years of journey from its first crystal to molecular structure.
Related PDB 3la4
Related UniProtKB
[39]
Resource
Comments
Medline ID
PubMed ID 21788478
Journal Proc Natl Acad Sci U S A
Year 2011
Volume 108
Pages 13095-9
Authors Carter EL, Tronrud DE, Taber SR, Karplus PA, Hausinger RP
Title Iron-containing urease in a pathogenic bacterium.
Related PDB 3qga 3qgk
Related UniProtKB
[40]
Resource
Comments
Medline ID
PubMed ID 21542631
Journal Acc Chem Res
Year 2011
Volume 44
Pages 520-30
Authors Zambelli B, Musiani F, Benini S, Ciurli S
Title Chemistry of Ni2+ in urease: sensing, trafficking, and catalysis.
Related PDB
Related UniProtKB

Comments
There are several types of urease enzymes based on the composition of subunits. This enzyme is composed of two subunits, one of which has a catalytic domain.
According to the literature, at least three catalytic mechanisms have been reported. Two mechanisms for hydrolysis, which proceeds through a tetrahedral intermediate (diaminohydroxymethanolate) that gives finally carbamate and ammonia (see [12], [17] and [20]). One mechanism for elimination, which proceeds through an intermediate, cyanic acid (see [23] and [28]).
(i) Hydrolysis by a reverse protonation mechanism: Carbonyl oxygen of urea is bound to Nickel-1, whereas a hydrolytic water is bound to Nickel-2. The hydrolytic water makes a nucleophilic attack on the carbonyl carbon of urea, forming a tetrahedral intermediate (diaminohydroxymethanolate). His322 (PDB;1e9y) acts as a general acid to protonate a leaving amino group, although the residue has a low pKa. Thus, carbamate and an ammonia can be produced. (see [12], [14], [19] and [20])
(ii) Hydrolysis by nucleophilic attack of a bridging hydroxide: Carbonyl oxygen of urea is bound to Nickel-1, whereas an amine group is bound to Nickel-2. The bridging hydroxide between the two nickel ions acts as a nucleophile, which attacks on the carbonyl carbon, forming a tetrahedral intermediate. The Asp residue, which is bound to Nickel-2, transfers proton from the hydroxyl group of the intermediate to the leaving amine group. His322 may stabilize the intermediate, rather than acting as a general acid. (see [17], [24], [33] and [40])
(iii) Elimination through cyanic acid (see [23], [28], [35], [36] and [37])
Alghough these reported mechanisms lead to a debate, the hydrolysis mechanism by bridging hydroxide seems to be the most reasonable, from structural viewpoints.

Created Updated
2005-10-18 2012-03-23