DB code: S00232

RLCP classification 4.12.642320.458 : Addition
5.201.2781500.453 : Elimination
CATH domain 3.20.20.140 : TIM Barrel Catalytic domain
E.C. 3.5.4.4
CSA 1a4l
M-CSA 1a4l
MACiE

CATH domain Related DB codes (homologues)
3.20.20.140 : TIM Barrel S00231 M00186 D00673 D00675 D00801 D00873 M00030 M00225 M00226

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P03958 Adenosine deaminase
EC 3.5.4.4
Adenosine aminohydrolase
NP_001258981.1 (Protein)
NM_001272052.1 (DNA/RNA sequence)
NP_031424.1 (Protein)
NM_007398.4 (DNA/RNA sequence)
PF00962 (A_deaminase)
[Graphical View]
P56658 Adenosine deaminase
EC 3.5.4.4
Adenosine aminohydrolase
NP_776312.1 (Protein)
NM_173887.2 (DNA/RNA sequence)
PF00962 (A_deaminase)
[Graphical View]

KEGG enzyme name
adenosine deaminase
deoxyadenosine deaminase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P03958 ADA_MOUSE Adenosine + H(2)O = inosine + NH(3).
P56658 ADA_BOVIN Adenosine + H(2)O = inosine + NH(3).

KEGG Pathways
Map code Pathways E.C.
MAP00230 Purine metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00212 C00001 C00294 C00014 I00018
E.C.
Compound Zinc Adenosine H2O Inosine NH3 6-Hydroxy-adenosine
Type heavy metal amine group,nucleoside H2O amide group,nucleoside amine group,organic ion
ChEBI 29105
16335
15377
17596
16134
PubChem 32051
60961
22247451
962
6021
222
1a4lA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Intermediate-analogue:DCF
1a4lB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Intermediate-analogue:DCF
1a4lC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Intermediate-analogue:DCF
1a4lD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Intermediate-analogue:DCF
1a4mA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Intermediate-analogue:PRH
1a4mB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Intermediate-analogue:PRH
1a4mC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Intermediate-analogue:PRH
1a4mD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Intermediate-analogue:PRH
1addA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Analogue:1DA Bound:HOH_461 Unbound Unbound Unbound
1fkwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Analogue:PUR Unbound Unbound Unbound
1fkxA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Intermediate-analogue:PRH
1uioA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Intermediate-analogue:HPR
1uipA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Analogue:PUR Unbound Unbound Unbound
2adaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Intermediate-analogue:HPR
1krmA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Intermediate-analogue:PRH
1ndvA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1ndwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1ndyA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1ndzA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1o5rA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1qxlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1umlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1v78A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1v79A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1v7aA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1w1iE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1w1iF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1w1iG Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1w1iH Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
2bgnE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
2bgnF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
2bgnG Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
2bgnH Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [10], [12], [14], [15], [27]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1a4lA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1a4lB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 717;HIS 738;ASP 795 HIS 515;HIS 517;HIS 714;ASP 795(Zinc binding)
1a4lC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 1217;HIS 1238;ASP 1295 HIS 1015;HIS 1017;HIS 1214;ASP 1295(Zinc binding)
1a4lD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 1717;HIS 1738;ASP 1795 HIS 1515;HIS 1517;HIS 1714;ASP 1795(Zinc binding)
1a4mA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1a4mB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 717;HIS 738;ASP 795 HIS 515;HIS 517;HIS 714;ASP 795(Zinc binding)
1a4mC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 1217;HIS 1238;ASP 1295 HIS 1015;HIS 1017;HIS 1214;ASP 1295(Zinc binding)
1a4mD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 1717;HIS 1738;ASP 1795 HIS 1515;HIS 1517;HIS 1714;ASP 1795(Zinc binding)
1addA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1fkwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238; HIS 15;HIS 17;HIS 214; (Zinc binding) mutant D295E
1fkxA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding) mutant D296A
1uioA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding) mutant H238A
1uipA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding) mutant H238E
2adaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1krmA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 214;HIS 235;ASP 292 HIS 12;HIS 14;HIS 211;ASP 292(Zinc binding)
1ndvA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1ndwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1ndyA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1ndzA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1o5rA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1qxlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1umlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1v78A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1v79A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1v7aA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1w1iE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1w1iF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1w1iG Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
1w1iH Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
2bgnE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
2bgnF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
2bgnG Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)
2bgnH Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 217;HIS 238;ASP 295 HIS 15;HIS 17;HIS 214;ASP 295(Zinc binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.8455-8456
[2]
p.7382-7383
[4]
p.1246-1247
[6]
Fig.4, p.1282-1283
[7]
p.7364-7365
[10]
Fig.3, p.1692-1693
[11]
p.693
[12]
[13]
Scheme 1
[14]
Fig.1, p.7863, p.7871
[15]
Fig.1, p.15027-15028
[19]
p.4974-4975
[20]
p.8322-8323
[22]
p.2589-2590

References
[1]
Resource
Comments
Medline ID
PubMed ID 3442668
Journal Biochemistry
Year 1987
Volume 26
Pages 8450-7
Authors Kurz LC, Frieden C
Title Adenosine deaminase converts purine riboside into an analogue of a reactive intermediate: a 13C NMR and kinetic study.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3427079
Journal Biochemistry
Year 1987
Volume 26
Pages 7378-84
Authors Weiss PM, Cook PF, Hermes JD, Cleland WW
Title Evidence from nitrogen-15 and solvent deuterium isotope effects on the chemical mechanism of adenosine deaminase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 3398052
Journal J Mol Biol
Year 1988
Volume 200
Pages 613-4
Authors Wilson DK, Rudolph FB, Harrison ML, Kellems RE, Quiocho FA
Title Preliminary X-ray analysis of crystals of murine adenosine deaminase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 2713361
Journal Biochemistry
Year 1989
Volume 28
Pages 1242-7
Authors Jones W, Kurz LC, Wolfenden R
Title Transition-state stabilization by adenosine deaminase: 1,6-addition of water to purine ribonucleoside, the enzyme's affinity for 6-hydroxy-1,6-dihydropurine ribonucleoside, and the effective concentration of substrate water at the active site.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 2275794
Journal J Biomol Struct Dyn
Year 1990
Volume 8
Pages 199-212
Authors Cox MB, Arjunan P, Arora SK
Title Structural and conformational analysis of pentostatin (2'-deoxycoformycin), a potent inhibitor of adenosine deaminase.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
Medline ID 92022516
PubMed ID 1925539
Journal Science
Year 1991
Volume 252
Pages 1278-84
Authors Wilson DK, Rudolph FB, Quiocho FA
Title Atomic structure of adenosine deaminase complexed with a transition-state analog: understanding catalysis and immunodeficiency mutations.
Related PDB 2ada
Related UniProtKB P03958
[7]
Resource
Comments
Medline ID
PubMed ID 1510925
Journal Biochemistry
Year 1992
Volume 31
Pages 7356-66
Authors Kati WM, Acheson SA, Wolfenden R
Title A transition state in pieces: major contributions of entropic effects to ligand binding by adenosine deaminase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 1731884
Journal Biochemistry
Year 1992
Volume 31
Pages 39-48
Authors Kurz LC, Moix L, Riley MC, Frieden C
Title The rate of formation of transition-state analogues in the active site of adenosine deaminase is encounter-controlled: implications for the mechanism.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 1518061
Journal J Mol Biol
Year 1992
Volume 226
Pages 917-21
Authors Sharff AJ, Wilson DK, Chang Z, Quiocho FA
Title Refined 2.5 A structure of murine adenosine deaminase at pH 6.0.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 8439534
Journal Biochemistry
Year 1993
Volume 32
Pages 1689-94
Authors Wilson DK, Quiocho FA
Title A pre-transition-state mimic of an enzyme: X-ray structure of adenosine deaminase with bound 1-deazaadenosine and zinc-activated water.
Related PDB 1add
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 7634072
Journal Nat Struct Biol
Year 1994
Volume 1
Pages 691-4
Authors Wilson DK, Quiocho FA
Title Crystallographic observation of a trapped tetrahedral intermediate in a metalloenzyme.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 8634299
Journal Biochemistry
Year 1996
Volume 35
Pages 1672-80
Authors Mohamedali KA, Kurz LC, Rudolph FB
Title Site-directed mutagenesis of active site glutamate-217 in mouse adenosine deaminase.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 8664259
Journal Biochemistry
Year 1996
Volume 35
Pages 4697-703
Authors Shih P, Wolfenden R
Title Enzyme-substrate complexes of adenosine and cytidine deaminases: absence of accumulation of water adducts.
Related PDB
Related UniProtKB
[14]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 8672487
Journal Biochemistry
Year 1996
Volume 35
Pages 7862-72
Authors Sideraki V, Mohamedali KA, Wilson DK, Chang Z, Kellems RE, Quiocho FA, Rudolph FB
Title Probing the functional role of two conserved active site aspartates in mouse adenosine deaminase.
Related PDB 1fkw 1fkx
Related UniProtKB
[15]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
Medline ID 97098127
PubMed ID 8942668
Journal Biochemistry
Year 1996
Volume 35
Pages 15019-28
Authors Sideraki V, Wilson DK, Kurz LC, Quiocho FA, Rudolph FB
Title Site-directed mutagenesis of histidine 238 in mouse adenosine deaminase: substitution of histidine 238 does not impede hydroxylate formation.
Related PDB 1uio 1uip
Related UniProtKB P03958
[16]
Resource
Comments
Medline ID
PubMed ID 9442929
Journal Biochem Mol Biol Int
Year 1997
Volume 43
Pages 1339-52
Authors Lupidi G, Marmocchi F, Venardi G, Cristalli G
Title Functional residues at the active site of bovine brain adenosine deaminase.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9361033
Journal Hum Mol Genet
Year 1997
Volume 6
Pages 2271-8
Authors Jiang C, Hong R, Horowitz SD, Kong X, Hirschhorn R
Title An adenosine deaminase (ADA) allele contains two newly identified deleterious mutations (Y97C and L106V) that interact to abolish enzyme activity.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 9341908
Journal J Med Chem
Year 1997
Volume 40
Pages 3336-45
Authors Groziak MP, Huan ZW, Ding H, Meng Z, Stevens WC, Robinson PD
Title Effect of a chemical modification on the hydrated adenosine intermediate produced by adenosine deaminase and a model reaction for a potential mechanism of action of 5-aminoimidazole ribonucleotide carboxylase.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9538015
Journal Biochemistry
Year 1998
Volume 37
Pages 4968-76
Authors Deng H, Kurz LC, Rudolph FB, Callender R
Title Characterization of hydrogen bonding in the complex of adenosine deaminase with a transition state analogue: a Raman spectroscopic study.
Related PDB
Related UniProtKB
[20]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
Medline ID 98285559
PubMed ID 9622483
Journal Biochemistry
Year 1998
Volume 37
Pages 8314-24
Authors Wang Z, Quiocho FA
Title Complexes of adenosine deaminase with two potent inhibitors: X-ray structures in four independent molecules at pH of maximum activity.
Related PDB 1a4l 1a4m
Related UniProtKB P03958
[21]
Resource
Comments
Medline ID
PubMed ID 9474762
Journal Biophys Chem
Year 1998
Volume 70
Pages 41-56
Authors Caiolfa VR, Gill D, Parola AH
Title Probing the active site of adenosine deaminase by a pH responsive fluorescent competitive inhibitor.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 10704207
Journal Biochemistry
Year 2000
Volume 39
Pages 2581-92
Authors Ford H Jr, Dai F, Mu L, Siddiqui MA, Nicklaus MC, Anderson L, Marquez VE, Barchi JJ Jr
Title Adenosine deaminase prefers a distinct sugar ring conformation for binding and catalysis: kinetic and structural studies.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 10673097
Journal Bioorg Med Chem Lett
Year 2000
Volume 10
Pages 139-41
Authors Tritsch D, Jung PM, Burger A, Biellmann JF
Title 3'-Beta-ethynyl and 2'-deoxy-3'-beta-ethynyl adenosines: first 3'-beta-branched-adenosines substrates of adenosine deaminase.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 12057661
Journal Bioorg Med Chem
Year 2002
Volume 10
Pages 2723-30
Authors Hernandez S, Ford H Jr, Marquez VE
Title Is the anomeric effect an important factor in the rate of adenosine deaminase catalyzed hydrolysis of purine nucleosides? A direct comparison of nucleoside analogues constructed on ribose and carbocyclic templates with equivalent heterocyclic bases selected to promote hydration.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 11901152
Journal J Biol Chem
Year 2002
Volume 277
Pages 19720-6
Authors Richard E, Alam SM, Arredondo-Vega FX, Patel DD, Hershfield MS
Title Clustered charged amino acids of human adenosine deaminase comprise a functional epitope for binding the adenosine deaminase complexing protein CD26/dipeptidyl peptidase IV.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 12437375
Journal J Biomol Struct Dyn
Year 2002
Volume 20
Pages 375-80
Authors Anderson E, Britt BM
Title The stability curve of bovine adenosine deaminase is bimodal.
Related PDB
Related UniProtKB
[27]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12554940
Journal Acta Crystallogr D Biol Crystallogr
Year 2003
Volume 59
Pages 299-303
Authors Kinoshita T, Nishio N, Nakanishi I, Sato A, Fujii T
Title Structure of bovine adenosine deaminase complexed with 6-hydroxy-1,6-dihydropurine riboside.
Related PDB 1krm
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 12643924
Journal Bioorg Med Chem Lett
Year 2003
Volume 13
Pages 1115-8
Authors Terasaka T, Nakanishi I, Nakamura K, Eikyu Y, Kinoshita T, Nishio N, Sato A, Kuno M, Seki N, Sakane K
Title Structure-based de novo design of non-nucleoside adenosine deaminase inhibitors.
Related PDB
Related UniProtKB
[29]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 14709046
Journal J Am Chem Soc
Year 2004
Volume 126
Pages 34-5
Authors Terasaka T, Kinoshita T, Kuno M, Nakanishi I
Title A highly potent non-nucleoside adenosine deaminase inhibitor: efficient drug discovery by intentional lead hybridization.
Related PDB 1ndv 1ndw 1ndy 1ndz
Related UniProtKB
[30]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15213224
Journal J Biol Chem
Year 2004
Volume 279
Pages 43330-5
Authors Weihofen WA, Liu J, Reutter W, Saenger W, Fan H
Title Crystal structure of CD26/dipeptidyl-peptidase IV in complex with adenosine deaminase reveals a highly amphiphilic interface.
Related PDB 1w1i
Related UniProtKB
[31]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15239652
Journal J Med Chem
Year 2004
Volume 47
Pages 3730-43
Authors Terasaka T, Kinoshita T, Kuno M, Seki N, Tanaka K, Nakanishi I
Title Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.
Related PDB 1o5r 1uml 1qxl
Related UniProtKB
[32]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15139750
Journal J Med Chem
Year 2004
Volume 47
Pages 2728-31
Authors Terasaka T, Okumura H, Tsuji K, Kato T, Nakanishi I, Kinoshita T, Kato Y, Kuno M, Seki N, Naoe Y, Inoue T, Tanaka K, Nakamura K
Title Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors.
Related PDB 1v78 1v79 1v7a
Related UniProtKB
[33]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15695814
Journal J Biol Chem
Year 2005
Volume [Epub ahead of print]
Pages [Epub ahead of print]
Authors Weihofen WA, Liu J, Reutter W, Saenger W, Fan H
Title Crystal structures of HIV-1 Tat derived nonapeptides Tat(1-9) and Trp2-Tat(1-9) bound to the active site of dipeptidyl peptidase IV (CD26).
Related PDB 2bgn
Related UniProtKB

Comments
This enzyme belongs to the adenosine and AMP deaminase family.
This enzyme is homologous to guanine deaminase (EC 3.5.4.3; D00873 in EzCatDB) and cytosine deaminase (EC 3.5.4.1; D00675 in EzCatDB), sharing a similar catalytic site.
This enzyme catalyzes two successive reactions (as in cytidine deaminase (D00406 in EzCatDB), according to the literature [6], [10] & [20].
(A) Additive double-bond deformation; Addition of water to purine C6-carbon to form a tetrahedral intermediate (I00018).
(B) Eliminative double-bond formation; Elimination of amine group from the intermediate, forming a carbonyl group.
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Although literature [10] suggested that His238 is a general base to activate the water in the first reaction (A), other papers gave the evidence against it. Instead of His238, Asp295 seems more likely base (see [6], [14] & [15]). Moreover, in the second reaction, some papers ([14] & [15]) suggested that His238 might act as a general acid to protonate the eliminated amine group, it is too distant from the group. Instead of the residue, hydrophobic cluster composed of Leu58, Phe61, Thr269 & Phe300 seems to facilitate the elimination (see [20]). However, these hydrophobic residues are not so conserved among the homologous enzymes (guanine deaminase and cytosine deaminase).
In analogy with cytosine deaminase (D00675 in EzCatDB), which adopts Fe2+ ion as cofactor, and guanine deaminase, which uses the same cofactor, zinc ion, as this enzyme, this enzyme may catalyzes the following reactions (addition and elimination):
(A) Additive double-bond deformation; Addition of water to purine C6-carbon, forming a tetrahedral intermediate (I00018):
(A1) Asp295 acts as a general base to deprotonate the Zinc-bound water. Here, the positive charge of His238 seems to stabilize the activated water.
(A2) The activated water makes a nucleophilic attack on the C6 atom, whilst Glu217 acts as a general acid to protonate the N1 atom (protonation site) of the purine. This reaction leads to the formation of tetrahedral intermediate at the C6 atom, transforming the N1-C6 bond from double bond to single bond (I00018).
(B) Eliminative double-bond formation; Elimination of amine group from the intermediate, forming a carbonyl group.
(B1) Asp295 acts as a general acid to protonate the eliminated amine group, releasing the ammonia.
(B2) Asp295 acts as a general base to deprotonate the hydroxyl group, bound to the zinc ion and His238. (Here, His238 may assist the catalytic function of Asp295 as well.) This reaction leads to the enol form of the product, inosine. (This may be an E1-like reaction, as amine elimination occurs prior to deprotonation.)

Created Updated
2005-03-22 2012-10-17