|CATH domain||Related DB codes (homologues)|
|126.96.36.199 : Urease, subunit C; domain 1||D00673,D00675,D00801,M00030,M00225,M00226|
|188.8.131.52 : TIM Barrel||S00231,S00232,M00186,D00673,D00675,D00801,M00030,M00225,M00226|
|Activity||Guanine + H(2)O = xanthine + NH(3).|
|Cofactor||Binds 1 zinc ion per subunit.|
|References for Catalytic Mechanism|
|References||Sections||No. of steps in catalysis|
|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.|
|Journal||Proc Natl Acad Sci U S A|
|Authors||Murphy PM, Bolduc JM, Gallaher JL, Stoddard BL, Baker D|
|Title||Alteration of enzyme specificity by computational loop remodeling and design.|
|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.|
|This enzyme is homologous to adenosine deaminase (EC 184.108.40.206; S00232 in EzCatDB) and cytosine deaminase (EC 220.127.116.11; 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 18.104.22.168; 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 ).
(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.