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Structural and mechanistic studies of AlkB
Author(s) -
Hunt John Francis,
Yu Bomina,
Ergel Burce,
Pastore Chiara,
Liebisch Gregory,
Edstrom William,
Gibney Brian,
Friesner Richard,
Farid Ramy
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.526.3
Subject(s) - alkb , enzyme , dna repair , dna , biochemistry , biology , computational biology , chemistry
Recently, there has been rapid progress in understanding the molecular functions of DNA repair enzymes in the AlkB superfamily, which are present in many eubacteria and all higher eukaryotes. These enzymes have been demonstrated to catalyze direct repair of adenine and cytosine bases that have been alkylated on endocyclic nitrogen atoms, a toxic DNA modification mediated by both endogenous and environmental mutagens. Elucidation of the chemical reaction catalyzed by AlkB has led to progress in understanding the physiological functions of the homologous enzymes, which include repair of damaged mRNA and tRNA molecules that reduce translation efficiency in addition to repair of mutagenic lesions in DNA. However, numerous features of AlkB superfamily enzymes remain to be characterized, including the biological functions of the 8 distinct sequence homologues conserved in mammalian organisms. This presentation will summarize the results of coordinated structural and mechanistic investigations of AlkB homologues. X‐ray crystallographic studies have provided insight into the catalytic reaction cycle of E. coli AlkB as well as the structural mechanisms underlying its ability to repair damage to chemically diverse nucleotide bases. These studies suggest a functional coupling between protein dynamics and enzyme turnover which is being investigated using experimental and computational techniques. Computational methods have also been used to identify inhibitors of AlkB which are being applied to studies of the physiological functions of the homologues human enzymes.