Reversible, partial inactivation of plant betaine aldehyde dehydrogenase by betaine aldehyde: mechanism and possible physiological implications

2016 ◽  
Vol 473 (7) ◽  
pp. 873-885 ◽  
Author(s):  
Andrés Zárate-Romero ◽  
Darío S. Murillo-Melo ◽  
Carlos Mújica-Jiménez ◽  
Carmina Montiel ◽  
Rosario A. Muñoz-Clares
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Cysteine Residue ◽  
Betaine Aldehyde Dehydrogenase ◽  
Short Term ◽  
Betaine Aldehyde ◽  
Partial Inactivation ◽  
Reversible Formation

The activity of plant BADH enzymes may be down-regulated in the short term by a novel and physiologically relevant mechanism, consisting of the reversible formation of a thiohemiacetal between a conserved non-essential cysteine residue and the substrate betaine aldehyde.

Novel NADPH–cysteine covalent adduct found in the active site of an aldehyde dehydrogenase

2011 ◽  
Vol 439 (3) ◽  
pp. 443-455 ◽  
Author(s):  
Ángel G. Díaz-Sánchez ◽  
Lilian González-Segura ◽  
Enrique Rudiño-Piñera ◽  
Alfonso Lira-Rocha ◽  
Alfredo Torres-Larios ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Aldehyde Dehydrogenase ◽  
Active Site ◽  
Cysteine Residue ◽  
Covalent Modification ◽  
Enzyme Inactivation ◽  
Betaine Aldehyde Dehydrogenase ◽  
Betaine Aldehyde ◽  
Oxidative Stresses ◽  
Covalent Adduct

PaBADH (Pseudomonas aeruginosa betaine aldehyde dehydrogenase) catalyses the irreversible NAD(P)+-dependent oxidation of betaine aldehyde to its corresponding acid, the osmoprotector glycine betaine. This reaction is involved in the catabolism of choline and in the response of this important pathogen to the osmotic and oxidative stresses prevalent in infection sites. The crystal structure of PaBADH in complex with NADPH showed a novel covalent adduct between the C2N of the pyridine ring and the sulfur atom of the catalytic cysteine residue, Cys286. This kind of adduct has not been reported previously either for a cysteine residue or for a low-molecular-mass thiol. The Michael addition of the cysteine thiolate in the ‘resting’ conformation to the double bond of the α,β-unsaturated nicotinamide is facilitated by the particular conformation of NADPH in the active site of PaBADH (also observed in the crystal structure of the Cys286Ala mutant) and by an ordered water molecule hydrogen bonded to the carboxamide group. Reversible formation of NAD(P)H–Cys286 adducts in solution causes reversible enzyme inactivation as well as the loss of Cys286 reactivity towards thiol-specific reagents. This novel covalent modification may provide a physiologically relevant regulatory mechanism of the irreversible PaBADH-catalysed reaction, preventing deleterious decreases in the intracellular NAD(P)+/NAD(P)H ratios.

Modulation of the reactivity of the essential cysteine residue of betaine aldehyde dehydrogenase from Pseudomonas aeruginosa

2002 ◽  
Vol 361 (3) ◽  
pp. 577-585 ◽  
Author(s):  
Lilian GONZÁLEZ-SEGURA ◽  
Roberto VELASCO-GARCÍA ◽  
Rosario A. MUÑOZ-CLARES
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Aldehyde Dehydrogenase ◽  
Ph Dependence ◽  
Catalytic Efficiency ◽  
Opportunistic Pathogen ◽  
Order Rate Constant ◽  
Cysteine Residue ◽  
Ion Pair ◽  
Betaine Aldehyde Dehydrogenase ◽  
Betaine Aldehyde

Betaine aldehyde dehydrogenase (BADH) catalyses the irreversible NAD(P)+-dependent oxidation of betaine aldehyde to glycine betaine. In the human opportunistic pathogen Pseudomonas aeruginosa this reaction is an obligatory step in the assimilation of carbon and nitrogen when bacteria are growing in choline or choline precursors. As with every aldehyde dehydrogenase studied so far, BADH possesses an essential cysteine residue involved in the formation of the intermediate thiohemiacetal with the aldehyde substrate. We report here that the chemical modification of this residue is conveniently measured by the loss in enzyme activity, which allowed us to explore its reactivity in a pH range around neutrality. The pH dependence of the observed second-order rate constant of BADH inactivation by methyl methanethiosulphonate (MMTS) suggests that at low pH values the essential cysteine residue exists as thiolate by the formation of an ion pair with a positively charged residue. The estimated macroscopic pK values are 8.6 and 4.0 for the free and ion-pair-forming thiolate respectively. The reactivity towards MMTS of both thiolate forms is notably lower than that of model compounds of similar pK, suggesting a considerable steric inhibition by the structure of the protein. Binding of the dinucleotides rapidly induced a significant and transitory increment of thiolate reactivity, followed by a relatively slow change to an almost unreactive form. Thus it seems that to gain protection against oxidation without compromising catalytic efficiency, BADH from P. aeruginosa has evolved a complex and previously undescribed mechanism, involving several conformational rearrangements of the active site, to suit the reactivity of the essential thiol to the availability of coenzyme and substrate.

Effect of the drug cyclophosphamide on the activity of porcine kidney betaine aldehyde dehydrogenase

2021 ◽  
Author(s):  
Ramses Cruz-Valencia ◽  
Aldo A. Arvizu-Flores ◽  
Jesús A. Rosas-Rodríguez ◽  
Elisa M. Valenzuela-Soto
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Betaine Aldehyde Dehydrogenase ◽  
Porcine Kidney ◽  
Betaine Aldehyde
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