| Autor: |
Clarke, Michael J., Goodenough, John B., Ibers, James A., Klixbüll Jørgensen, C., Neilands, Joe B., Reinen, Dirk, Weiss, Raymond, Williams, Robert Joseph P., Connett, P. H., Folłmann, H., Lammers, M., Mann, S., Odom, J. D., Wetterhahn, K. E., Lammers, Manfred, Follmann, Hartmut |
| Zdroj: |
Inorganic Elements in Biochemistry; 1983, p27-91, 65p |
| Abstrakt: |
Reductive elimination of the 2′-hydroxyl group from ribonucleotides to yield 2′-deoxyribonucleotides, the monomeric precursors of DNA, requires an uncommon type of enzyme catalysis in which the transition metals, manganese, iron, or cobalt, and free radical intermediates cooperate. In the group of deoxyadenosylcobalamin (coenzyme B 12)-dependent ribonucleotide reductases the coenzyme supplies a transient radical pair of deoxyadenosyl· and cob(II)alamin whereas in the nonheme-iron group of enzymes a protein subunit carries a stable tyrosyl radical coordinated to a binuclear iron(III) complex; the manganese-dependent enzymes are less precisely known. The radicals are thought to function in hydrogen transfer from cysteine SH to the ribonucleotide substrate, and the metal complexes are apparently needed to generate and stabilize the radicals. In aerobic organisms oxygen also plays a critical role in these processes and hence in DNA synthesis and cell proliferation. In addition to the transition metals, Mg2+ or Ca2+ are required by several ribonucleotide reductases for structural integrity. However the most potent inhibitors of deoxy-ribonucleotide biosynthesis (of potential interest in chemotherapy) are not metal chelators but radical scavengers. Cell cycle arrest and cell death produced by simple chemicals like N-hydroxyurea and hydroxamates can be traced back to their reaction with ribonucleotide reductase. Evidence is accumulating that independent enzymes of deoxyribonucleotide and DNA synthesis are functionally coupled in a novel type of supramolecular structure. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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