| Structural highlights
Function
GLDA_ECOLI Catalyzes the NAD-dependent oxidation of glycerol to dihydroxyacetone (glycerone). Allows microorganisms to utilize glycerol as a source of carbon under anaerobic conditions. In E.coli, an important role of GldA is also likely to regulate the intracellular level of dihydroxyacetone by catalyzing the reverse reaction, i.e. the conversion of dihydroxyacetone into glycerol. Possesses a broad substrate specificity, since it is also able to oxidize 1,2-propanediol and to reduce glycolaldehyde, methylglyoxal and hydroxyacetone into ethylene glycol, lactaldehyde and 1,2-propanediol, respectively.[1] [2] [3] [4]
Publication Abstract from PubMed
During glycerol metabolism, the initial step of glycerol oxidation is catalysed by glycerol dehydrogenase (GDH), which converts glycerol to dihydroxyacetone in a NAD(+) -dependent manner via an ordered Bi-Bi kinetic mechanism. Structural studies conducted with GDH from various species have mainly elucidated structural details of the active site and ligand binding. However, the structure of the full GDH complex with both cofactor and substrate bound is not determined, and thus, the structural basis of the kinetic mechanism of GDH remains unclear. Here, we report the crystal structures of Escherichia coli GDH with a substrate analogue bound in the absence or presence of NAD(+) . Structural analyses including molecular dynamics simulations revealed that GDH possesses a flexible beta-hairpin, and that during the ordered progression of the kinetic mechanism, the flexibility of the beta-hairpin is reduced after NAD(+) binding. It was also observed that this alterable flexibility of the beta-hairpin contributes to the cofactor binding and possibly to the catalytic efficiency of GDH. These findings suggest the importance of the flexible beta-hairpin to GDH enzymatic activity and shed new light on the kinetic mechanism of GDH.
Structural and functional insights into the flexible beta-hairpin of glycerol dehydrogenase.,Park T, Hoang HN, Kang JY, Park J, Mun SA, Jin M, Yang J, Jung CH, Eom SH FEBS J. 2023 May 11. doi: 10.1111/febs.16813. PMID:37165682[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Subedi KP, Kim I, Kim J, Min B, Park C. Role of GldA in dihydroxyacetone and methylglyoxal metabolism of Escherichia coli K12. FEMS Microbiol Lett. 2008 Feb;279(2):180-7. doi:, 10.1111/j.1574-6968.2007.01032.x. Epub 2007 Dec 20. PMID:18179582 doi:http://dx.doi.org/10.1111/j.1574-6968.2007.01032.x
- ↑ Gonzalez R, Murarka A, Dharmadi Y, Yazdani SS. A new model for the anaerobic fermentation of glycerol in enteric bacteria: trunk and auxiliary pathways in Escherichia coli. Metab Eng. 2008 Sep;10(5):234-45. Epub 2008 May 27. PMID:18632294 doi:http://dx.doi.org/S1096-7176(08)00020-7
- ↑ Tang CT, Ruch FE Jr, Lin CC. Purification and properties of a nicotinamide adenine dinucleotide-linked dehydrogenase that serves an Escherichia coli mutant for glycerol catabolism. J Bacteriol. 1979 Oct;140(1):182-7. PMID:40950
- ↑ Truniger V, Boos W. Mapping and cloning of gldA, the structural gene of the Escherichia coli glycerol dehydrogenase. J Bacteriol. 1994 Mar;176(6):1796-800. PMID:8132480
- ↑ Park T, Hoang HN, Kang JY, Park J, Mun SA, Jin M, Yang J, Jung CH, Eom SH. Structural and functional insights into the flexible β-hairpin of glycerol dehydrogenase. FEBS J. 2023 May 11. PMID:37165682 doi:10.1111/febs.16813
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