4GQG

Crystal structure of AKR1B10 complexed with NADP+

Summary for 4GQG

• Entry DOI: 10.2210/pdb4gqg/pdb
• Descriptor: Aldo-keto reductase family 1 member B10, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• Functional Keywords: alpha-beta tim barrel, nadp-dependant oxidoreductase, nadp+, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: O60218
• Total number of polymer chains: 1
• Total formula weight: 37041.16

Authors

Zhang, L.,Zheng, X.,Chen, S.,Zhai, J.,Hu, X. (deposition date: 2012-08-23, release date: 2013-08-28, Last modification date: 2023-11-08)

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 (1.92 Å)