Abstract
Gre2 is a key enzyme in the methylglyoxal detoxification pathway; it uses NADPH or NADH as an electron donor to reduce the cytotoxic methylglyoxal to lactaldehyde. This enzyme is a member of the short-chain dehydrogenase/reductase (SDR) superfamily whose members catalyze this type of reaction with a broad range of substrates. To elucidate the structural features, we determined the crystal structures of the NADPH-dependent methylglyoxal reductase Gre2 from Candida albicans (CaGre2) for both the apo-form and NADPH-complexed form at resolutions of 2.8 and 3.02 Å, respectively. The CaGre2 structure is composed of two distinct domains: the N-terminal cofactor-binding domain and the C-terminal substrate-binding domain. Extensive comparison of CaGre2 with its homologous structures reveals conformational changes in α12 and β3′ of the NADPH-complex forms. This study may provide insights into the structural and functional variation of SDR family proteins.
Highlights
Gre2 is a key enzyme in the methylglyoxal detoxification pathway; it uses NADPH or NADH as an electron donor to reduce the cytotoxic methylglyoxal to lactaldehyde
Based on the processed data, the CaGre2 crystal volume per protein mass (VM ) was 3.69 Å3 /Da. These results indicate that an asymmetric unit of CaGre2 contains only one molecule, with 66.7% solvent content [18,22]
The crystallographic state of CaGre2 was consistent with the results of size-exclusion chromatography (SEC) performance and with the PISA evaluation [23]
Summary
Gre is a key enzyme in the methylglyoxal detoxification pathway; it uses NADPH or NADH as an electron donor to reduce the cytotoxic methylglyoxal to lactaldehyde. This enzyme is a member of the short-chain dehydrogenase/reductase (SDR) superfamily whose members catalyze this type of reaction with a broad range of substrates. Methylglyoxal (MG; CH3 COCHO) is an extremely toxic compound to a wide variety of cells from microorganisms to mammals and plants It acts as an inhibitor of cell division and is associated with a range of biological effects, including microtubule assembly, protein synthesis, and carcinogenicity [1,2]. Accumulation of MG causes damage to nucleic acids and proteins in eukaryotic cells by irreversibly forming advanced glycation end products during glucose and fructose catalytic metabolism and producing bioactive free radicals [5,6,7]
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