4JIR

Crystal Structure Of Aldose Reductase (AKR1B1) Complexed With NADP+ And Epalrestat

Summary for 4JIR

• Entry DOI: 10.2210/pdb4jir/pdb
• Related: 4GQ0 4GQG 4I5X 4JIH 4JII
• Descriptor: Aldose reductase, {5-[(2E)-2-methyl-3-phenylprop-2-en-1-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl}acetic acid, SULFATE ION, ... (5 entities in total)
• Functional Keywords: tim barrel, oxidoreductase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P15121
• Total number of polymer chains: 1
• Total formula weight: 37153.27

Authors

Zhang, L.,Zheng, X.,Zhang, H.,Zhao, Y.,Chen, K.,Zhai, J.,Hu, X. (deposition date: 2013-03-06, release date: 2013-10-23, Last modification date: 2024-02-28)

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 Å)