PDBsum entry: 1wkq

Hydrolase

PDB id: 1wkq

Contents

Protein chains

158 a.a. *

Ligands

IMD ×2

Metals

_ZN ×2

Waters ×450

* Residue conservation analysis

PDB id:

1wkq

Name:

Hydrolase

Title:

Crystal structure of bacillus subtilis guanine deaminase. The first domain-swapped structure in the cytidine deaminase superfamily

Structure:

Guanine deaminase. Chain: a, b. Synonym: guanase, guanine aminase, guanine aminohydrolase, gah, gdease. Engineered: yes

Source:

Bacillus subtilis. Organism_taxid: 1423. Gene: guanine deaminase. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.17Å R-factor: 0.161 R-free: 0.177

Authors:

S.H.Liaw,Y.J.Chang,C.T.Lai

Key ref:

S.H.Liaw et al. (2004). Crystal structure of Bacillus subtilis guanine deaminase: the first domain-swapped structure in the cytidine deaminase superfamily. J Biol Chem, 279, 35479-35485. PubMed id: 15180998 DOI: 10.1074/jbc.M405304200

Date:

01-Jun-04 Release date: 13-Jul-04

Protein chains

O34598  (GUAD_BACSU) -  Guanine deaminase

Seq: 156 a.a.

Struc: 158 a.a.

Enzyme reactions

• Enzyme class: E.C.3.5.4.3 - Guanine deaminase.
• Reaction: Guanine + H₂O = xanthine + NH₃

Guanine (Bound ligand (Het Group name = IMD) matches with 45.00% similarity) + H(2)O = xanthine + NH(3)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Biological process: purine base metabolic process (1 term)
• Biochemical function: catalytic activity (5 terms)

Added reference

DOI no: 10.1074/jbc.M405304200

J Biol Chem 279:35479-35485 (2004)

PubMed id: 15180998

Crystal structure of Bacillus subtilis guanine deaminase: the first domain-swapped structure in the cytidine deaminase superfamily.

S.H.Liaw, Y.J.Chang, C.T.Lai, H.C.Chang, G.G.Chang.

ABSTRACT

Guanine deaminase, a key enzyme in the nucleotide metabolism, catalyzes the hydrolytic deamination of guanine into xanthine. The crystal structure of the 156-residue guanine deaminase from Bacillus subtilis has been solved at 1.17-A resolution. Unexpectedly, the C-terminal segment is swapped to form an intersubunit active site and an intertwined dimer with an extensive interface of 3900 A(2) per monomer. The essential zinc ion is ligated by a water molecule together with His(53), Cys(83), and Cys(86). A transition state analog was modeled into the active site cavity based on the tightly bound imidazole and water molecules, allowing identification of the conserved deamination mechanism and specific substrate recognition by Asp(114) and Tyr(156'). The closed conformation also reveals that substrate binding seals the active site entrance, which is controlled by the C-terminal tail. Therefore, the domain swapping has not only facilitated the dimerization but has also ensured specific substrate recognition. Finally, a detailed structural comparison of the cytidine deaminase superfamily illustrates the functional versatility of the divergent active sites found in the guanine, cytosine, and cytidine deaminases and suggests putative specific substrate-interacting residues for other members such as dCMP deaminases.

Selected figure(s)

Figure 2.
FIG. 2. Structure of bGD. Ribbon views of the monomer (A) and dimer (B). The tightly bound zinc ion is shown as a sphere with its ligands, the general base glutamate, and the transition-state intermediate analogue (DHX) as ball-and-stick representations. The protein is a three-layered / / structure with a central -sheet sandwiched on either side by -helices. The dimer is made up of one monomer colored in red, and the other colored in green (Fig. 2B was created with a similar orientation to Fig. 3C). Single letter amino acid abbreviations are used with position numbers in panel A.

Figure 3.
FIG. 3. The active site of bGD. A, the 2F[o] - F[c] electron density map of the active site contoured at a 3 level and shown in cyan, and the difference anomalous map for the zinc ion contoured at a 20 level and shown in purple. The densities of the bound imidazole and the three water molecules (W1-W3) are highlighted in green. The active site residues and the imidazole are shown as ball-and-stick representations, and the modeled inhibitor (DHX) as magenta sticks. The zinc ion and the water molecules as magenta and red spheres, respectively. B, stereo view of the interaction networks in the active site. There are nine direct hydrogen bonds between the protein molecule and the inhibitor (see "Results and Discussion" for a detailed explanation). C, molecular surfaces of one bGD subunit are colored for electrostatic potential from -10 k[B] T (red) to 10 k[B]T (blue), whereas the surfaces of the other subunit are displayed explicitly as worms. The zinc ion is embedded at the deepest part, whereas the inhibitor lies near the cavity opening (Fig. 3C was created with a similar orientation to Fig. 2B). Single letter amino acid abbreviations are used with position numbers.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 35479-35485) copyright 2004.

Figures were selected by an automated process.