Crystal Structure of the Tetrameric Cytidine Deaminase from Bacillus subtilis at 2.0 Å Resolution
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- 作者：Eva Johansson ; Nina Mejlhede ; Jan Neuhard ; and Sine Larsen
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：February 26, 2002
- 年：2002
- 卷：41
- 期：8
- 页码：2563 - 2570
- 全文大小：737K
- 年卷期：v.41,no.8(February 26, 2002)
- ISSN：1520-4995
文摘
Cytidine deaminases (CDA, EC 3.5.4.5) are zinc-containing enzymes in the pyrimidine salvagepathway 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 isassembled of four identical subunits with one active site apiece. The subunit of D-CDA is composed oftwo domains each exhibiting the same fold as the T-CDA subunits, but only one of them contains zincin the active site. The similarity results in a conserved structural core in the two CDA forms. An intriguingdifference between the two CDA structures is the zinc coordinating residues found at the N-terminal oftwo 
-helices: three cysteine residues in the tetrameric form and two cysteine residues and one histidineresidue in the dimeric form. The role of the zinc ion is to activate a water molecule and thereby generatea hydroxide ion. How the zinc ion in T-CDA surrounded with three negatively charged residues cancreate a similar activity of T-CDA compared to D-CDA has been an enigma. However, the structure ofT-CDA reveals that the negative charge caused by the three ligands is partly neutralized by (1) an arginineresidue hydrogen-bonded to two of the cysteine residues and (2) the dipoles of two -helices.
-helices: three cysteine residues in the tetrameric form and two cysteine residues and one histidineresidue in the dimeric form. The role of the zinc ion is to activate a water molecule and thereby generatea hydroxide ion. How the zinc ion in T-CDA surrounded with three negatively charged residues cancreate a similar activity of T-CDA compared to D-CDA has been an enigma. However, the structure ofT-CDA reveals that the negative charge caused by the three ligands is partly neutralized by (1) an arginineresidue hydrogen-bonded to two of the cysteine residues and (2) the dipoles of two -helices.