9OU1

Crystal structure of maize AKR4C13 in P21 space group

Replaces:  5JGY

Summary for 9OU1

• Entry DOI: 10.2210/pdb9ou1/pdb
• Descriptor: Aldose reductase, AKR4C13, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: aldo-keto reductase superfamily, akr4c subfamily, oxidoreductase
• Biological source: Zea mays
• Total number of polymer chains: 2
• Total formula weight: 75705.35

Authors

Santos, M.L.,Giuseppe, P.O.,Kiyota, E.,Schmelz, E.A.,Yunes, J.A.,Koch, K.E.,Murakami, M.T.,Aparicio, R.,Sousa, S.M. (deposition date: 2025-05-28, release date: 2025-07-02, Last modification date: 2025-07-30)

Primary citation

Morais de Sousa, S.,Oliveira de Giuseppe, P.,Murakami, M.T.,Guan, J.C.,Saunders, J.W.,Kiyota, E.,Santos, M.L.,Schmelz, E.A.,Yunes, J.A.,Koch, K.E.
Functional genomics and structural insights into maize aldo-keto reductase-4 family: Stress metabolism and substrate specificity in embryos.
J.Biol.Chem., 301:110404-110404, 2025

PubMed Abstract: Aldo-keto reductases (AKRs) are ubiquitous in nature and are able to reduce a wide range of substrates, from simple sugars to potentially toxic aldehydes. In plants, AKRs are involved in key metabolic processes including reactive aldehyde detoxification. This study aimed to i) delineate a maize gene family encoding Aldo Keto Reductase-4s (AKR4s) ii) help bridge sequence-to-function gaps among them, and iii) focus on a family member implicated in embryo specific stress metabolism. We employed a genome-wide analysis approach to identify maize genes encoding AKR4s, defining and annotating a 15-member gene family that clustered into three subgroups. Expression profiling, validated through wet lab experiments, revealed distinct functional roles: i) AKR4C Zm-1 functions in aldehyde detoxification during stress, ii) AKR4C Zm-2 includes stress-responsive AKRs with diverse substrate affinities, and iii) AKR4A/B Zm-3 contributes to specialized metabolites like phytosiderophores for iron transport. To investigate the impact of sequence variation on function, we characterized ZmAKR4C13, a representative of AKR4C Zm-1. Its mRNA and protein were predominantly localized in embryos, suggesting a specialized role. Recombinant ZmAKR4C13 efficiently reduced methylglyoxal and small aldehydes but showed poor activity toward aldoses larger than four carbons. Crystallographic analysis identified a size constraint at the active site, attributed to the bulkier LEU residue at position 294. Collectively, our results emphasize how subtle modifications in active-site architecture influence AKR substrate specificity. They also demonstrate a potential role of maize ZmAKR4C13 in detoxifying methylglyoxal and other small metabolites that could contribute to stress signaling in embryos.

PubMed: 40544997
DOI: 10.1016/j.jbc.2025.110404

Experimental method

X-RAY DIFFRACTION (1.45 Å)