Download Aldehyde Dehydrogenase Presentation

Aldehyde
Dehydrogenase
Zach Lawton
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Background
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Superfamily of Nictonamide adenine dinucleotide phosphate (NADP)
enzymes
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Location: all three domains of life
 Three subclasses of enzymes in eukaryotes
 Cytosol, mitochondria, endoplasmic reticulum and cornea
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Function: catalyze aldehyde to carboxylic acid
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Importance:
 Metabolism
 Removal of toxic aldehydes
 UV damage to the cornea
 Hangovers
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Amino Acid Sequence Alignment
Lys 192
Cys 302
Glu 268
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Structure—ALDH2
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Expressed as tetramer or octamer in
most cases.
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Mitochondria ALDH2 shown.
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Percentage of alpha helix and beta
sheets vary between each protein and
class of ALDH.
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ALDH1 ALDH2
 ~40% α-helix, ~35% β-sheet
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ALDH3
 ~35% α-helix, ~5% β-sheet
Alpha Helix – Yellow
Beta Sheet – Blue
PDB = 1O05
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Active Site—ALDH1 and ALDH2
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NAD(P)+ binds into the pocket
where it is stabilized by Lys192.
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Interactions with Cys302 and
Glu268.
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Mg2+ is used as a catalysis.
Miller, S.J., Hurley, T.D. (2003) Coenzyme Isomerization is
Intergral to Catalysis in Aldehyde. ACS Biochemistry. 42,
7100-7109.
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Reaction Mechanism
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Conclusion
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ALDH is a NAD/P+ Enzyme superfamily.
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Primary function: Converts aldehyde to carboxylic acid using Cystine and
Glutamate residues.
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Three Subclasses
 ALDH1
 Cytosol
 ALDH2
 Mitochondria, Endoplasmic reticulum
 ALDH3
 Cornea and Liver
QUESTIONS?
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