Crystal Structure of the Tetrameric Cytidine Deaminase from Bacillus subtilis at 2.0 Å Resolution

Cytidine deaminases (CDA, EC 3.5.4.5) are zinc-containing enzymes in the pyrimidine salvage pathway that catalyze the formation of uridine and deoxyuridine from cytidine and deoxycytidine, respectively. Two different classes have been identified in the CDA family, a homodimeric form (D-CDA) with two...

Full description

Saved in:
Bibliographic Details
Published in:Biochemistry (Easton) 2002-02, Vol.41 (8), p.2563-2570
Main Authors: Johansson, Eva, Mejlhede, Nina, Neuhard, Jan, Larsen, Sine
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Bacillus subtilis
Bacillus subtilis - enzymology
Binding Sites
Biopolymers - chemistry
Crystallography, X-Ray
Cytidine Deaminase - chemistry
Hydrogen Bonding
Models, Molecular
Molecular Sequence Data
Protein Conformation
Sequence Homology, Amino Acid
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cytidine deaminases (CDA, EC 3.5.4.5) are zinc-containing enzymes in the pyrimidine salvage pathway that catalyze the formation of uridine and deoxyuridine from cytidine and deoxycytidine, respectively. Two different classes have been identified in the CDA family, a homodimeric form (D-CDA) with two zinc ions per dimer and a homotetrameric form (T-CDA) with four zinc ions per tetramer. We have determined the first structure of a T-CDA from Bacillus subtilis. The active form of T-CDA is assembled of four identical subunits with one active site apiece. The subunit of D-CDA is composed of two domains each exhibiting the same fold as the T-CDA subunits, but only one of them contains zinc in the active site. The similarity results in a conserved structural core in the two CDA forms. An intriguing difference between the two CDA structures is the zinc coordinating residues found at the N-terminal of two α-helices:  three cysteine residues in the tetrameric form and two cysteine residues and one histidine residue in the dimeric form. The role of the zinc ion is to activate a water molecule and thereby generate a hydroxide ion. How the zinc ion in T-CDA surrounded with three negatively charged residues can create a similar activity of T-CDA compared to D-CDA has been an enigma. However, the structure of T-CDA reveals that the negative charge caused by the three ligands is partly neutralized by (1) an arginine residue hydrogen-bonded to two of the cysteine residues and (2) the dipoles of two α-helices.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi011849a