CBR3: Human Carbonyl Reductase
PDB Code: 2HRB
Human carbonyl reductase (CBR) activity accounts for a significant fraction of the metabolism of endogenous and xenobiotic carbonyl compounds such as prostaglandins, steroids, and various pharmacological agents. CBRs are members of the family of short-chain dehydrogenases/reductases. In humans, there are two monomeric carbonyl reductases, carbonyl reductase 1 (CBR1) and carbonyl reductase 3 (CBR3), which are encoded by different genes located 62 kilobases apart on chromosome 21 (CBR1 and CBR3). CBR1 and CBR3 share 72% identity and 79% similarity at the amino acid level.
Despite the prominent role of CBR1 mediated drug metabolism, there have been few reports on the catalytic properties of CBR3 since the identification of the gene in 1998, in particular no endogenous substrate has been identified up to date. Several studies have described a wide range of variability in the metabolism of drugs that are CBR substrates, which may contribute to the largely unpredictable pharmacokinetics and pharmacodynamics of anthracyclines in adult and pediatric cancer patients. It is possible that genetic polymorphisms in CBR1 and CBR3 are the key for the variability in the disposition of CBR drug substrates.
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