ALDH2: Difference between revisions

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ALDH2 enzyme functions as homotetramer where each monomer consists of two Rossmann fold domains and an oligomerization tail. NAD+ binds to one of the Rossmann folds in the gap between αF and αG helices while leaving pyrophosphate exposed to the solvent. <ref name="nov2020">DOI: 10.1016/j.ebiom.2020.102753</ref> <ref>DOI:10.1016/j.cbi.2012.12.009</ref>

Active site consists of highly conserved Cys-302, Asn-169 and Glu-268 catalytic triad. Cys-302 acting as nucleophile and covalently binding the metabolized aldehyde. Formed thiohemiacetal is stabilized by Asn-169 and hydride is transferred to substrate NAD+. It is agreed upon, that role of Glu-268 is to mediate attack of water molecule on the acyl-sulfur bond.<ref>doi: 10.1016/s0969-2126(97)00224-4. PMID: 9195888.</ref> Thr-244 is also highly conserved residue, as it plays role in hydride transfer between substrates. Substitution of this amino acid results in decrease of catalytic efficiency.<ref>doi: 10.1016/j.cbi.2012.12.009</ref> Another conserved residues are Arg84, Lys192, Thr384, Glu399, Ser471, Glu398 and Lys489, all of them negatively effecting catalysis when substituted.<ref>doi: 10.1074/jbc.272.30.18817. PMID: 9228056</ref>

Active site consists of highly conserved Cys-302, Asn-169 and Glu-268 catalytic triad. Cys-302 acting as nucleophile and covalently binding the metabolized aldehyde. Formed thiohemiacetal is stabilized by Asn-169 and hydride is transferred to substrate NAD+. It is agreed upon, that role of Glu-268 is to mediate attack of water molecule on the acyl-sulfur bond.<ref>doi: 10.1016/s0969-2126(97)00224-4. PMID: 9195888</ref> Thr-244 is also highly conserved residue, as it plays role in hydride transfer between substrates. Substitution of this amino acid results in decrease of catalytic efficiency.<ref>doi: 10.1016/j.cbi.2012.12.009</ref> Another conserved residues are Arg84, Lys192, Thr384, Glu399, Ser471, Glu398 and Lys489, all of them negatively effecting catalysis when substituted.<ref>doi: 10.1074/jbc.272.30.18817. PMID: 9228056</ref>

</StructureSection>

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 <StructureSection load='3N80' size='300' side='right' caption='Human mitochondrial aldehyde dehydrogenase, apo form (PDB entry [http://doi.org/10.2210/pdb3N80/pdb 3N80])' scene=''>
 ALDH2 enzyme functions as homotetramer where each monomer consists of two Rossmann fold domains and an oligomerization tail. NAD+ binds to one of the Rossmann folds in the gap between αF and αG helices while leaving pyrophosphate exposed to the solvent. <ref name="nov2020">DOI: 10.1016/j.ebiom.2020.102753</ref> <ref>DOI:10.1016/j.cbi.2012.12.009</ref>
-Active site consists of highly conserved Cys-302, Asn-169 and Glu-268 catalytic triad. Cys-302 acting as nucleophile and covalently binding the metabolized aldehyde. Formed thiohemiacetal is stabilized by Asn-169 and hydride is transferred to substrate NAD+. It is agreed upon, that role of Glu-268 is to mediate attack of water molecule on the acyl-sulfur bond.<ref>doi: 10.1016/s0969-2126(97)00224-4. PMID: 9195888.</ref> Thr-244 is also highly conserved residue, as it plays role in hydride transfer between substrates. Substitution of this amino acid results in decrease of catalytic efficiency.<ref>doi: 10.1016/j.cbi.2012.12.009</ref> Another conserved residues are Arg84, Lys192, Thr384, Glu399, Ser471, Glu398 and Lys489, all of them negatively effecting catalysis when substituted.<ref>doi: 10.1074/jbc.272.30.18817. PMID: 9228056</ref>
+Active site consists of highly conserved Cys-302, Asn-169 and Glu-268 catalytic triad. Cys-302 acting as nucleophile and covalently binding the metabolized aldehyde. Formed thiohemiacetal is stabilized by Asn-169 and hydride is transferred to substrate NAD+. It is agreed upon, that role of Glu-268 is to mediate attack of water molecule on the acyl-sulfur bond.<ref>doi: 10.1016/s0969-2126(97)00224-4. PMID: 9195888</ref> Thr-244 is also highly conserved residue, as it plays role in hydride transfer between substrates. Substitution of this amino acid results in decrease of catalytic efficiency.<ref>doi: 10.1016/j.cbi.2012.12.009</ref> Another conserved residues are Arg84, Lys192, Thr384, Glu399, Ser471, Glu398 and Lys489, all of them negatively effecting catalysis when substituted.<ref>doi: 10.1074/jbc.272.30.18817. PMID: 9228056</ref>
 </StructureSection>