Inhibition, crystal structures, and in-solution oligomeric structure of aldehyde dehydrogenase 9A1

Wyatt, Jesse W.; Korasick, David A.; Qureshi, Insaf Ahmed; Campbell, A.C.; Gates, Kent S.; Tanner, John J.

doi:10.1016/j.abb.2020.108477

Cited by 17 publications

(17 citation statements)

References 63 publications

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“…Among the selected 22 proteins, the highest-ranking protein was ALDH9A1(IMean ratio of 2.301), and the second was PRDX3 (IMean ratio of 2.095). ALDH9A1 belongs to the aldehyde dehydrogenase family of proteins [ 23 ]. However, we did not observe any changes in the Control, EAU or EAU + ICA group ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Icariin alleviates uveitis by targeting peroxiredoxin 3 to modulate retinal microglia M1/M2 phenotypic polarization

Wang

et al. 2022

Redox Biology

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Section: Resultsmentioning

confidence: 99%

Icariin alleviates uveitis by targeting peroxiredoxin 3 to modulate retinal microglia M1/M2 phenotypic polarization

Wang

et al. 2022

Redox Biology

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“…50–60 kDa, and are composed of 450–500 amino acids. ALDHs exist as dimers [ 1 ], tetramers [ 2 , 3 , 4 ] and hexamers [ 5 ]; however, the latter are less prevalent, with only two resolved structures available to date [ 6 , 7 , 8 ]. Their structures consist of three conserved domains, the catalytic domain, the cofactor binding domain, and the oligomerisation domain [ 1 ], which work together to catalyse the conversion of an aldehyde substrate using NAD(P) + cofactor to form the corresponding carboxylic acid and NAD(P)H. Additionally, some ALDHs can act as esterases [ 9 , 10 ] or can reduce nitrate [ 11 ], indicating that this family of enzymes possess broad catalytic properties.…”

Section: Introductionmentioning

confidence: 99%

Study of ALDH from Thermus thermophilus—Expression, Purification and Characterisation of the Non-Substrate Specific, Thermophilic Enzyme Displaying Both Dehydrogenase and Esterase Activity

Shortall

Durack

Magner

et al. 2021

Cells

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Aldehyde dehydrogenases (ALDH), found in all kingdoms of life, form a superfamily of enzymes that primarily catalyse the oxidation of aldehydes to form carboxylic acid products, while utilising the cofactor NAD(P)+. Some superfamily members can also act as esterases using p-nitrophenyl esters as substrates. The ALDHTt from Thermus thermophilus was recombinantly expressed in E. coli and purified to obtain high yields (approximately 15–20 mg/L) and purity utilising an efficient heat treatment step coupled with IMAC and gel filtration chromatography. The use of the heat treatment step proved critical, in its absence decreased yield of 40% was observed. Characterisation of the thermophilic ALDHTt led to optimum enzymatic working conditions of 50 °C, and a pH of 8. ALDHTt possesses dual enzymatic activity, with the ability to act as a dehydrogenase and an esterase. ALDHTt possesses broad substrate specificity, displaying activity for a range of aldehydes, most notably hexanal and the synthetic dialdehyde, terephthalaldehyde. Interestingly, para-substituted benzaldehydes could be processed efficiently, but ortho-substitution resulted in no catalytic activity. Similarly, ALDHTt displayed activity for two different esterase substrates, p-nitrophenyl acetate and p-nitrophenyl butyrate, but with activities of 22.9 and 8.9%, respectively, compared to the activity towards hexanal.

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“…Only the AMP portion of bound NADP + was clearly visible in the cryo-EM map, while there was no density for the rest of the cofactor. Of note, weak density for the nicotinamide riboside of NAD + and NADP + is commonly observed in aldehyde dehydrogenases 27 , 43 , 44 .…”

Section: Resultsmentioning

confidence: 99%

Structure of putative tumor suppressor ALDH1L1

et al. 2022

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Putative tumor suppressor ALDH1L1, the product of natural fusion of three unrelated genes, regulates folate metabolism by catalyzing NADP+-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO2. Cryo-EM structures of tetrameric rat ALDH1L1 revealed the architecture and functional domain interactions of this complex enzyme. Highly mobile N-terminal domains, which remove formyl from 10-formyltetrahydrofolate, undergo multiple transient inter-domain interactions. The C-terminal aldehyde dehydrogenase domains, which convert formyl to CO2, form unusually large interfaces with the intermediate domains, homologs of acyl/peptidyl carrier proteins (A/PCPs), which transfer the formyl group between the catalytic domains. The 4′-phosphopantetheine arm of the intermediate domain is fully extended and reaches deep into the catalytic pocket of the C-terminal domain. Remarkably, the tetrameric state of ALDH1L1 is indispensable for catalysis because the intermediate domain transfers formyl between the catalytic domains of different protomers. These findings emphasize the versatility of A/PCPs in complex, highly dynamic enzymatic systems.

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Inhibition, crystal structures, and in-solution oligomeric structure of aldehyde dehydrogenase 9A1

Cited by 17 publications

References 63 publications

Icariin alleviates uveitis by targeting peroxiredoxin 3 to modulate retinal microglia M1/M2 phenotypic polarization

Icariin alleviates uveitis by targeting peroxiredoxin 3 to modulate retinal microglia M1/M2 phenotypic polarization

Study of ALDH from Thermus thermophilus—Expression, Purification and Characterisation of the Non-Substrate Specific, Thermophilic Enzyme Displaying Both Dehydrogenase and Esterase Activity

Structure of putative tumor suppressor ALDH1L1

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