DB code: D00873

RLCP classification 5.201.2781500.453 : Elimination
4.12.642320.458 : Addition
CATH domain 2.30.40.10 : Urease, subunit C; domain 1
3.20.20.140 : TIM Barrel Catalytic domain
E.C. 3.5.4.3
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.20.20.140 : TIM Barrel S00231 S00232 M00186 D00673 D00675 D00801 M00030 M00225 M00226
2.30.40.10 : Urease, subunit C; domain 1 D00673 D00675 D00801 M00030 M00225 M00226

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
Q9Y2T3 Guanine deaminase
Guanase
Guanine aminase
EC 3.5.4.3
Guanine aminohydrolase
GAH
p51-nedasin
NP_001229434.1 (Protein)
NM_001242505.2 (DNA/RNA sequence)
NP_001229435.1 (Protein)
NM_001242506.2 (DNA/RNA sequence)
NP_001229436.1 (Protein)
NM_001242507.2 (DNA/RNA sequence)
NP_004284.1 (Protein)
NM_004293.4 (DNA/RNA sequence)
M38.981 (Metallo)
PF01979 (Amidohydro_1)
[Graphical View]

KEGG enzyme name
Guanine deaminase
Guanase
Guanine aminase
GAH

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q9Y2T3 GUAD_HUMAN Guanine + H(2)O = xanthine + NH(3). Homodimer. Binds 1 zinc ion per subunit.

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

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00242 C00001 C00385 C00014 I00149
E.C.
Compound Zinc guanine H2O xanthine NH3 2-hydroxy-guanine
Type heavy metal amide group,amine group,aromatic ring (with nitrogen atoms) H2O amide group,aromatic ring (with nitrogen atoms) amine group,organic ion
ChEBI 29105
16235
15377
17712
48517
16134
PubChem 32051
764
22247451
962
1188
222
2uz9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
3e0lA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
3e0lB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
4aqlA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
2uz9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Bound:XAN Unbound Unbound
3e0lA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
3e0lB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
4aqlA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Analogue:TXC Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature[2]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
2uz9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
3e0lA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
3e0lB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
4aqlA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2uz9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 243;HIS 279;ASP 330 HIS 82;HIS 84;HIS 240;ASP 330(Zinc binding)
3e0lA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 241;HIS 277;ASP 328 HIS 82;HIS 84;HIS 238;ASP 328(Zinc binding)
3e0lB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 241;HIS 277;ASP 328 HIS 82;HIS 84;HIS 238;ASP 328(Zinc binding)
4aqlA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 243;HIS 279;ASP 330 HIS 82;HIS 84;HIS 240;ASP 330(Zinc binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]

References
[1]
Resource
Comments
Medline ID
PubMed ID 17803218
Journal Proteins
Year 2008
Volume 70
Pages 873-81
Authors Fernandez JR, Welsh WJ, Firestein BL
Title Structural characterization of the zinc binding domain in cytosolic PSD-95 interactor (cypin): Role of zinc binding in guanine deamination and dendrite branching.
Related PDB 2i9u
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 19470646
Journal Proc Natl Acad Sci U S A
Year 2009
Volume 106
Pages 9215-20
Authors Murphy PM, Bolduc JM, Gallaher JL, Stoddard BL, Baker D
Title Alteration of enzyme specificity by computational loop remodeling and design.
Related PDB 3e0l
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 22662200
Journal PLoS One
Year 2012
Volume 7
Pages e37724
Authors Egeblad L, Welin M, Flodin S, Graslund S, Wang L, Balzarini J, Eriksson S, Nordlund P
Title Pan-pathway based interaction profiling of FDA-approved nucleoside and nucleobase analogs with enzymes of the human nucleotide metabolism.
Related PDB 4aql
Related UniProtKB

Comments
This enzyme is homologous to adenosine deaminase (EC 3.5.4.4; S00232 in EzCatDB) and cytosine deaminase (EC 3.5.4.1; D00675 in EzCatDB), sharing a similar active site. This enzyme and adenosine deaminase use zinc ion as cofactor, whereas cytosine deaminase adopts Fe2+ (Ferrous ion) as cofactor.
On the other hand, this enzyme is not homologous to the bacterial guanase (EC 3.5.4.3; S00810 in EzCatDB).
As this enzyme seems to have the same catalytic site with those homologous enzymes, the reaction mechanism can be similar to those by homologues. Thus, this enzyme catalyzes two successive reactions (rather than hydrolysis) as follows:
(A) Addition of water to imine carbon to form a tetrahedral intermediate (I00149).
(A1) Asp330 acts as a general base to deprotonate the zinc-bound water. Here, the positive charge of His279 seems to stabilize the activated water. His279 may assist the catalytic function of Glu243 as well (see D00675 literature [12]).
(A2) The activated water makes a nucleophilic attack on the C2 atom of guanine, whilst Glu243 acts as a general acid to protonate the N3 atom (protonation site) of the guanine. This reaction leads to the formation of tetrahedral intermediate at the C2 atom, transforming N3-C2 bond from a double bond to a single bond (I00149).
(B) Elimination of amine group from the intermediate (I00149), forming a carbonyl group.
(B1) Asp330 acts as a general acid to protonate the eliminated amine group, releasing the ammonia.
(B2) Asp330 acts as a general base to deprotonate the hydroxyl group, bound to the zinc ion and His279. (Here, His279 may assist the catalytic function of Asp330 as well.) This reaction leads to the enol form of the product, xanthine.

Created Updated
2012-10-09 2012-10-17