1k70
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The Structure of Escherichia coli Cytosine Deaminase bound to 4-Hydroxy-3,4-Dihydro-1H-Pyrimidin-2-one
OverviewOverview
Cytosine deaminase (CD) catalyzes the deamination of cytosine, producing, uracil. This enzyme is present in prokaryotes and fungi (but not, multicellular eukaryotes) and is an important member of the pyrimidine, salvage pathway in those organisms. The same enzyme also catalyzes the, conversion of 5-fluorocytosine to 5-fluorouracil; this activity allows the, formation of a cytotoxic chemotherapeutic agent from a non-cytotoxic, precursor. The enzyme is of widespread interest both for antimicrobial, drug design and for gene therapy applications against tumors. The, structure of Escherichia coli CD has been determined in the presence and, absence of a bound mechanism-based inhibitor. The enzyme forms an, (alphabeta)(8) barrel structure with structural similarity to adenosine, deaminase, a relationship that is undetectable at the sequence level, and, no similarity to bacterial cytidine deaminase. The enzyme is packed into a, hexameric assembly stabilized by a unique domain-swapping interaction, between enzyme subunits. The active site is located in the mouth of the, enzyme barrel and contains a bound iron ion that coordinates a hydroxyl, nucleophile. Substrate binding involves a significant conformational, change that sequesters the reaction complex from solvent.
About this StructureAbout this Structure
1K70 is a Single protein structure of sequence from Escherichia coli with FE and HPY as ligands. Active as Cytosine deaminase, with EC number 3.5.4.1 Full crystallographic information is available from OCA.
ReferenceReference
The structure of Escherichia coli cytosine deaminase., Ireton GC, McDermott G, Black ME, Stoddard BL, J Mol Biol. 2002 Jan 25;315(4):687-97. PMID:11812140
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