HIS 61;HIS 63;HIS 214;ASP 313(Fe2+ binding)
Atomic structure of adenosine deaminase complexed with a transition-state analog: understanding catalysis and immunodeficiency mutations.
A pre-transition-state mimic of an enzyme: X-ray structure of adenosine deaminase with bound 1-deazaadenosine and zinc-activated water.
Cytosine deaminase. The roles of divalent metal ions in catalysis.
Complexes of adenosine deaminase with two potent inhibitors: X-ray structures in four independent molecules at pH of maximum activity.
Escherichia coli cytosine deaminase: the kinetics and thermodynamics for binding of cytosine to the apoenzyme and the Zn(2+) holoenzyme are similar.
The structure of Escherichia coli cytosine deaminase.
Crystal structure of yeast cytosine deaminase. Insights into enzyme mechanism and evolution.
X-RAY CRYSTALLOGRAPHY (1.14 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG AND ZINC IONS, AND SUBUNIT.
The 1.14 A crystal structure of yeast cytosine deaminase: evolution of nucleotide salvage enzymes and implications for genetic chemotherapy.
Metal-mediated deamination of cytosine: experiment and DFT calculations.
Alanine-scanning mutagenesis reveals a cytosine deaminase mutant with altered substrate preference.
Random mutagenesis and selection of Escherichia coli cytosine deaminase for cancer gene therapy.
Three-dimensional structure and catalytic mechanism of cytosine deaminase.
Rescue of the orphan enzyme isoguanine deaminase.
This enzyme is homologous to adenosine deaminase (EC 3.5.4.4; S00232 in EzCatDB) and guanine deaminase (EC 3.5.4.3; D00873 in EzCatDB). Although its catalytic site is similar to those of the homologous enzymes, cofactor ion, Fe2+, is different from the cofactor ion, zinc ion, adopted by the homologous enzymes. However, the reaction mechanism seems to be very similar to those homologous enzymes. According to the literature [12] and the reaction mechanism of the homologous enzymes(S00232 and D00873 in EzCatDB), this enzyme catalyzes two successive reactions (rather than hydrolysis) as follows: (A) Addition of water to imine carbon to form a tetrahedral intermediate (I00151). (A1) Asp313 (or Glu217) acts as a general base to deprotonate the Fe2+-bound water. Here, the positive charge of His246 seems to stabilize the activated water. His246 may assist the catalytic function of Glu217 as well (see [12]). (A2) The activated water makes a nucleophilic attack on the C4 atom of cytosine, whilst Glu217 acts as a general acid to protonate the N3 atom (protonation site) of the cytosine. This reaction leads to the formation of tetrahedral intermediate at the C4 atom, transforming N3-C4 bond from a double bond to a single bond (I00151). (B) Elimination of amine group from the intermediate (I00151), forming a carbonyl group. (B1) Asp313 acts as a general acid to protonate the eliminated amine group, releasing the ammonia. (B2) Asp313 acts as a general base to deprotonate the hydroxyl group, bound to the Fe2+ ion and His246. (Here, His246 may assist the catalytic function of Asp313 as well.) This reaction leads to the enol form of the product, cytosine. (This may be an E1-like reaction, as amine elimination occurs prior to deprotonation.)