Human High-Km, Aldehyde Dehydrogenase (ALDH3): Molecular, Kinetic and Structural Features

Yin, Shih‐Jiun; Wang, Sung-Ling; Liao, Chin-Shya; Jörnvall, Hans

doi:10.1007/978-1-4615-2904-0_11

Cited by 9 publications

(3 citation statements)

References 35 publications

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“…A similar pattern appears to exist for Vh.ALDH, although the extent of N-terminal truncation is less than with class 3 ALDHs. Functionally, the longer N-terminal domains are suggested to be required for tetramer formation (Loomes & Jomvall, 1991) consistent with Vh.ALDH and other NADP+-utilizing ALDHs, whose structures are known to be dimeric (Evces & Lindahl, 1989;Lindahl et al, 1985;Lindahl & Evces, 1984;Sreerama & Sladek, 1993;Yin et al" 1993).…”

Section: Discussionmentioning

confidence: 99%

Involvement of cysteine 289 in the catalytic activity of an NADP+-specific fatty aldehyde dehydrogenase from Vibrio harveyi

Vedadi¹,

Szittner²,

Smillie³

et al. 1995

Biochemistry

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Fatty aldehyde dehydrogenase (Vh.ALDH) from the luminescent bacterium, Vibrio harveyi, may be implicated in controlling luminescence as it catalyzes the oxidation of the fatty aldehyde substrate for the light-emitting reaction. On the basis of the amino-terminal sequence of Vh.ALDH, a degenerate probe was used to screen a genomic library of V harveyi in pBR322, a positive clone was selected containing the Vh.ALDH gene and expressed in Escherichia coli, and the enzyme was purified to homogeneity. Although the sequence of the V. harveyi ALDH significantly diverged from other aldehyde dehydrogenases, mutation of a conserved cysteine implicated in catalysis completely inactivated the enzyme without loss of its ability to bind nucleotides, consistent with a catalytic role for this residue. Using absorption and fluorescence assays for NAD(P)H, it was shown that NAD+ and NADP+ bound to the same site and that saturation of Vh.ALDH with NADP+ occurred with a Michaelis constant (Km = 1.4 microM) over 40 times lower than that reported for other aldehyde dehydrogenases. Although V. harveyi aldehyde dehydrogenase is unique in terms of its high specificity for NADP+, the identification of a catalytic conserved cysteine in Vh.ALDH clearly indicates that a highly related mechanism and structure have been retained among even the most diverged aldehyde dehydrogenases.

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Section: Discussionmentioning

confidence: 99%

Involvement of cysteine 289 in the catalytic activity of an NADP+-specific fatty aldehyde dehydrogenase from Vibrio harveyi

Vedadi¹,

Szittner²,

Smillie³

et al. 1995

Biochemistry

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“…The upper portion of the substrate-binding tunnel is significantly more hydrophobic in ALDH C relative to Ec-ALDH and likely serves to restrict the polarity of substrates while favoring long-chain aldehydes 15,33,47,48 (Fig. 4, center left panel).…”

Section: Comparative Structural Analysis Of the Substrate-binding Tunnelmentioning

confidence: 95%

Structural and Biochemical Characterization of a Novel Aldehyde Dehydrogenase Encoded by the Benzoate Oxidation Pathway in Burkholderia xenovorans LB400

Bains

Boulanger

2008

Journal of Molecular Biology

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“…This similarity is consistent with the observed dimeric structure of the V. har eyi enzyme as well as the kinetic properties and substrate specificities. Both enzymes exhibit higher V max \K m values for increasing aldehyde chain length, suggesting the existence of a hydrophobic pocket at the active site that selects for longer-chain aldehydes [7][8][9]. Among the invariant amino acids there is only one conserved cysteine residue : Cys-302 from the class-1 and -2 mammalian enzymes, Cys-243 from the class-3 enzyme and Cys-289 in the enzyme from V. har eyi.…”

Section: Introductionmentioning

confidence: 99%

Crystal structure of the NADP+-dependent aldehyde dehydrogenase from Vibrio harveyi: structural implications for cofactor specificity and affinity

Ahvazi

Coulombe

Delarge

et al. 2000

Biochemical Journal

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Aldehyde dehydrogenase from the bioluminescent bacterium, Vibrio harveyi, catalyses the oxidation of long-chain aliphatic aldehydes to acids. The enzyme is unique compared with other forms of aldehyde dehydrogenase in that it exhibits a very high specificity and affinity for the cofactor NADP(+). Structural studies of this enzyme and comparisons with other forms of aldehyde dehydrogenase provide the basis for understanding the molecular features that dictate these unique properties and will enhance our understanding of the mechanism of catalysis for this class of enzyme. The X-ray structure of aldehyde dehydrogenase from V. harveyi has been solved to 2.5-A resolution as a partial complex with the cofactor NADP(+) and to 2. 1-A resolution as a fully bound 'holo' complex. The cofactor preference exhibited by different forms of the enzyme is predominantly determined by the electrostatic environment surrounding the 2'-hydroxy or the 2'-phosphate groups of the adenosine ribose moiety of NAD(+) or NADP(+), respectively. In the NADP(+)-dependent structures the presence of a threonine and a lysine contribute to the cofactor specificity. In the V. harveyi enzyme an arginine residue (Arg-210) contributes to the high cofactor affinity through a pi stacking interaction with the adenine ring system of the cofactor. Further differences between the V. harveyi enzyme and other aldehyde dehydrogenases are seen in the active site, in particular a histidine residue which is structurally conserved with phosphorylating glyceraldehyde-3-phosphate dehydrogenase. This may suggest an alternative mechanism for activation of the reactive cysteine residue for nucleophilic attack.

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Human High-Km, Aldehyde Dehydrogenase (ALDH3): Molecular, Kinetic and Structural Features

Cited by 9 publications

References 35 publications

Involvement of cysteine 289 in the catalytic activity of an NADP+-specific fatty aldehyde dehydrogenase from Vibrio harveyi

Involvement of cysteine 289 in the catalytic activity of an NADP+-specific fatty aldehyde dehydrogenase from Vibrio harveyi

Structural and Biochemical Characterization of a Novel Aldehyde Dehydrogenase Encoded by the Benzoate Oxidation Pathway in Burkholderia xenovorans LB400

Crystal structure of the NADP+-dependent aldehyde dehydrogenase from Vibrio harveyi: structural implications for cofactor specificity and affinity

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