Structural highlights
Function
ALDR_HUMAN Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Publication Abstract from PubMed
The antineoplastic target aldo-keto reductase family member 1B10 (AKR1B10) and the critical polyol pathway enzyme aldose reductase (AKR1B1) share high structural similarity. Crystal structures reported here reveal a surprising Trp112 native conformation stabilized by a specific Gln114-centered hydrogen bond network in the AKR1B10 holoenzyme, and suggest that AKR1B1 inhibitors could retain their binding affinities toward AKR1B10 by inducing Trp112 flip to result in an "AKR1B1-like" active site in AKR1B10, while selective AKR1B10 inhibitors can take advantage of the broader active site of AKR1B10 provided by the native Trp112 side-chain orientation.
Inhibitor selectivity between aldo-keto reductase superfamily members AKR1B10 and AKR1B1: Role of Trp112 (Trp111).,Zhang L, Zhang H, Zhao Y, Li Z, Chen S, Zhai J, Chen Y, Xie W, Wang Z, Li Q, Zheng X, Hu X FEBS Lett. 2013 Oct 4. pii: S0014-5793(13)00726-6. doi:, 10.1016/j.febslet.2013.09.031. PMID:24100137[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang L, Zhang H, Zhao Y, Li Z, Chen S, Zhai J, Chen Y, Xie W, Wang Z, Li Q, Zheng X, Hu X. Inhibitor selectivity between aldo-keto reductase superfamily members AKR1B10 and AKR1B1: Role of Trp112 (Trp111). FEBS Lett. 2013 Oct 4. pii: S0014-5793(13)00726-6. doi:, 10.1016/j.febslet.2013.09.031. PMID:24100137 doi:http://dx.doi.org/10.1016/j.febslet.2013.09.031
