4I5X

Crystal Structure Of AKR1B10 Complexed With NADP+ And Flufenamic acid

Summary for 4I5X

• Entry DOI: 10.2210/pdb4i5x/pdb
• Related: 4GQ0 4GQG
• Descriptor: Aldo-keto reductase family 1 member B10, 2-[[3-(TRIFLUOROMETHYL)PHENYL]AMINO] BENZOIC ACID, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• Functional Keywords: tim barrel, aldo-keto reductase, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: O60218
• Total number of polymer chains: 1
• Total formula weight: 37306.39

Authors

Zhang, L.,Zheng, X.,Chen, S.,Zhai, J.,Zhang, H.,Zhao, Y. (deposition date: 2012-11-29, release date: 2013-10-23, Last modification date: 2024-04-03)

Primary citation

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., 587:3681-3686, 2013

PubMed Abstract: 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.

PubMed: 24100137
DOI: 10.1016/j.febslet.2013.09.031

Experimental method

X-RAY DIFFRACTION (2.1 Å)