1jtk
Crystal structure of cytidine deaminase from Bacillus subtilis in complex with the inhibitor tetrahydrodeoxyuridine
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OverviewOverview
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 alpha-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, alpha-helices.
About this StructureAbout this Structure
1JTK is a Single protein structure of sequence from Bacillus subtilis with ZN and THU as ligands. Active as Cytidine deaminase, with EC number 3.5.4.5 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the tetrameric cytidine deaminase from Bacillus subtilis at 2.0 A resolution., Johansson E, Mejlhede N, Neuhard J, Larsen S, Biochemistry. 2002 Feb 26;41(8):2563-70. PMID:11851403
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