DB code: S00461

RLCP classification	1.40.14550.574 : Hydrolysis
CATH domain	3.90.245.10 : Inosine-uridine Nucleoside N-ribohydrolase; Chain A	Catalytic domain
E.C.	3.2.2.-
CSA	1mas
M-CSA	1mas
MACiE	M0039

CATH domain	Related DB codes (homologues)
3.90.245.10 : Inosine-uridine Nucleoside N-ribohydrolase; Chain A	S00751 S00910

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	Pfam
P83851	Inosine-uridine preferring nucleoside hydrolase	IU-nucleoside hydrolase IU-NH EC 3.2.2.- Purine nucleosidase Non-specific nucleoside hydrolase	PF01156 (IU_nuc_hydro) [Graphical View]
Q27546	Inosine-uridine preferring nucleoside hydrolase	IU-nucleoside hydrolase IU-NH EC 3.2.2.- Purine nucleosidase Non-specific nucleoside hydrolase	PF01156 (IU_nuc_hydro) [Graphical View]

KEGG enzyme name
inosine-uridine preferring nucleoside hydrolase IU-NH IU-nucleoside hydrolase non-specific nucleoside hydrolase purine nucleosidase

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
P83851	IUNH_LEIMA	A purine nucleoside + H(2)O = D-ribose + a purine base.	Homotetramer.		Calcium.
Q27546	IUNH_CRIFA	A purine nucleoside + H(2)O = D-ribose + a purine base.	Homotetramer.		Calcium.

KEGG Pathways
Map code	Pathways	E.C.
MAP00230	Purine metabolism
MAP00760	Nicotinate and nicotinamide metabolism

Compound table
	Cofactors	Substrates		Products		Intermediates
KEGG-id	C00076	C15586	C00001	C15587	C00121
E.C.
Compound	Calcium	N-D-Ribosylpurine	H2O	Purine	D-Ribose
Type	divalent metal (Ca2+, Mg2+)	nucleoside	H2O	aromatic ring (with nitrogen atoms)	carbohydrate
ChEBI	29108 29108	18255 18255	15377 15377	17258 35586 35588 35589 17258 35586 35588 35589	47013 47013
PubChem	271 271	68368 68368	22247451 962 22247451 962	1044 1044	5779 5779

1ezrA	Bound:_CA	Unbound		Unbound	Unbound
1ezrB	Bound:_CA	Unbound		Unbound	Unbound
1ezrC	Bound:_CA	Unbound		Unbound	Unbound
1ezrD	Bound:_CA	Unbound		Unbound	Unbound
1masA	Analogue:__K	Unbound		Unbound	Unbound
1masB	Analogue:__K	Unbound		Unbound	Unbound
2masA	Bound:_CA	Analogue:PIR		Unbound	Unbound
2masB	Bound:_CA	Analogue:PIR		Unbound	Unbound
2masC	Bound:_CA	Analogue:PIR		Unbound	Unbound
2masD	Bound:_CA	Analogue:PIR		Unbound	Unbound

Reference for Active-site residues
resource	references	E.C.

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

1ezrA	ASP 10;HIS 82;HIS 240	ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)
1ezrB	ASP 10;HIS 82;HIS 240	ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)
1ezrC	ASP 10;HIS 82;HIS 240	ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)
1ezrD	ASP 10;HIS 82;HIS 240	ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)
1masA	ASP 10; ;HIS 241	ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)			invisible H82
1masB	ASP 10; ;HIS 241	ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)			invisible H82
2masA	ASP 10;HIS 82;HIS 241	ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
2masB	ASP 10;HIS 82;HIS 241	ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
2masC	ASP 10;HIS 82;HIS 241	ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
2masD	ASP 10;HIS 82;HIS 241	ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[2]	p.5968-5970, Fig.7
[3]	p.5979
[4]	p.21717-21719
[5]	p.3533-3534
[6]	Fig.1, p.6279, p.6283	2
[7]	p.21117-21120
[9]	p.1368-1375
[10]	p.15943-15944, p.15945
[11]	Scheme 1, p.8830-8833	2
[12]	Scheme 1, p.14598-14600	2

References
[1]
Resource
Comments
Medline ID
PubMed ID	7577992
Journal	Biochemistry
Year	1995
Volume	34
Pages	13961-6
Authors	Parkin DW, Schramm VL
Title	Binding modes for substrate and a proposed transition-state analogue of protozoan nucleoside hydrolase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID	8634237
Journal	Biochemistry
Year	1996
Volume	35
Pages	5963-70
Authors	Gopaul DN, Meyer SL, Degano M, Sacchettini JC, Schramm VL
Title	Inosine-uridine nucleoside hydrolase from Crithidia fasciculata. Genetic characterization, crystallization, and identification of histidine 241 as a catalytic site residue.
Related PDB
Related UniProtKB
[3]
Resource
Comments	X-ray crystallography (2.5 Angstroms)
Medline ID
PubMed ID	8634238
Journal	Biochemistry
Year	1996
Volume	35
Pages	5971-5981
Authors	Degano M, Gopaul DN, Scapin G, Schramm VL, Sacchettini JC
Title	Three-dimensional structure of the inosine-uridine nucleoside N-ribohydrolase from Crithidia fasciculata.
Related PDB	1mas
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID	8702965
Journal	J Biol Chem
Year	1996
Volume	271
Pages	21713-9
Authors	Parkin DW
Title	Purine-specific nucleoside N-ribohydrolase from Trypanosoma brucei brucei. Purification, specificity, and kinetic mechanism.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID	9132003
Journal	Biochemistry
Year	1997
Volume	36
Pages	3528-34
Authors	Parkin DW, Limberg G, Tyler PC, Furneaux RH, Chen XY, Schramm VL
Title	Isozyme-specific transition state inhibitors for the trypanosomal nucleoside hydrolases.
Related PDB
Related UniProtKB
[6]
Resource
Comments	X-ray crystallography (2.3 Angstroms)
Medline ID
PubMed ID	9572842
Journal	Biochemistry
Year	1998
Volume	37
Pages	6277-6285
Authors	Degano M, Almo SC, Sacchettini JC, Schramm VL
Title	Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor.
Related PDB	2mas
Related UniProtKB
[7]
Resource
Comments	X-ray crystallography (2.5 Angstroms)
Medline ID
PubMed ID	10409664
Journal	J Biol Chem
Year	1999
Volume	274
Pages	21114-21120
Authors	Shi W, Schramm VL, Almo SC
Title	Nucleoside hydrolase from Leishmania major. Cloning, expression, catalytic properties, transition state inhibitors, and the 2.5-a crystal structure.
Related PDB	1ezr
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID	11282633
Journal	Appl Environ Microbiol
Year	2001
Volume	67
Pages	1783-7
Authors	Ogawa J, Takeda S, Xie SX, Hatanaka H, Ashikari T, Amachi T, Shimizu S
Title	Purification, characterization, and gene cloning of purine nucleosidase from Ochrobactrum anthropi.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID	11292348
Journal	J Mol Biol
Year	2001
Volume	307
Pages	1363-79
Authors	Versees W, Decanniere K, Pelle R, Depoorter J, Brosens E, Parkin DW, Steyaert J
Title	Structure and function of a novel purine specific nucleoside hydrolase from Trypanosoma vivax.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID	11854281
Journal	J Biol Chem
Year	2002
Volume	277
Pages	15938-46
Authors	Versees W, Decanniere K, Van Holsbeke E, Devroede N, Steyaert J
Title	Enzyme-substrate interactions in the purine-specific nucleoside hydrolase from Trypanosoma vivax.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID	12137535
Journal	J Am Chem Soc
Year	2002
Volume	124
Pages	8825-33
Authors	Mazumder D, Kahn K, Bruice TC
Title	Computer simulations of trypanosomal nucleoside hydrolase: determination of the protonation state of the bound transition-state analogue.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID	12465969
Journal	J Am Chem Soc
Year	2002
Volume	124
Pages	14591-600
Authors	Mazumder D, Bruice TC
Title	Exploring nucleoside hydrolase catalysis in silico: molecular dynamics study of enzyme-bound substrate and transition state.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the IU-nuceloside hydrolase family. This enzyme is homologous to ribosylpyrimidine nucleosidase (EC 3.2.2.8; S00751 in EzCatDB). According to the literature [2] & [4], The oxocarbonium ion is formed in the transition state, which is characterstic of an SN1-like catalytic mechanism. The paper [3] on crystal structure suggested that His241 can act as proton donor for the leaving nitrogenous base, whilst the paper [5] mentioned that His82 as well as His241 can protonates the leaving group. Asp14 is reported to have a hydrogen-bonding interaction with His241 [3]. Moreover, the papers [5], [6] and [7] suggested that metal or Ca2+ -bound water can attack the C1' atom after the oxocarbonium ion has been formed. One of the aspartic acid residues, Asp10, Asp15, Thr126 and Asp242, is proposed to be the group which will act as a general base, extracting the proton from the incoming water nucleophile, according to the paper [3]. The paper [12] based on molecular simulation suggested that the proton will be transferred from the activated water through Asp10 to Asp15 to water pool.

Comments

This enzyme belongs to the IU-nuceloside hydrolase family. This enzyme is homologous to ribosylpyrimidine nucleosidase (EC 3.2.2.8; S00751 in EzCatDB).
According to the literature [2] & [4], The oxocarbonium ion is formed in the transition state, which is characterstic of an SN1-like catalytic mechanism.
The paper [3] on crystal structure suggested that His241 can act as proton donor for the leaving nitrogenous base, whilst the paper [5] mentioned that His82 as well as His241 can protonates the leaving group. Asp14 is reported to have a hydrogen-bonding interaction with His241 [3].
Moreover, the papers [5], [6] and [7] suggested that metal or Ca2+ -bound water can attack the C1' atom after the oxocarbonium ion has been formed. One of the aspartic acid residues, Asp10, Asp15, Thr126 and Asp242, is proposed to be the group which will act as a general base, extracting the proton from the incoming water nucleophile, according to the paper [3]. The paper [12] based on molecular simulation suggested that the proton will be transferred from the activated water through Asp10 to Asp15 to water pool.

Created	Updated
2002-07-11	2011-09-27