Sandbox Reserved 1475: Difference between revisions
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[[Image:Figure 3.png|thumb|upright=1.5| [[Figure 3]] Section (a) is the dimer of RalDH2 with the green spheres representing the amino and carboy termini of the substrate access channel loop. Section (b) shows the same orientation as section (a) with both dimers present and then the two dimers spun 90 degrees on the X-axis.<ref name="Lamb AL, Newcomber ME" /> ]] | [[Image:Figure 3.png|thumb|upright=1.5| [[Figure 3]] Section (a) is the dimer of RalDH2 with the green spheres representing the amino and carboy termini of the substrate access channel loop. Section (b) shows the same orientation as section (a) with both dimers present and then the two dimers spun 90 degrees on the X-axis.<ref name="Lamb AL, Newcomber ME" /> ]] | ||
[[Image:catalytic sites.png|thumb|upright=1.5| [[Figure4]] Chain D of RalDH2 with Cys-302 in yellow, Glu-268 in green, and Asn-187 in red. Image modified in and taken from Chimera from (PDB entry [[1bi9]])]] | |||
The structure was based on the mitochondrial aldehyde dehydrogenase type two. RalDH2 in a monomer made up of 3 domains: a nucleotide-binding domain (1-136, 161-270), a catalytic domain (271-484), and a tetramerization domain (137-160, 485-484) as shown in [[Figure 1]].<ref name="Lamb AL, Newcomber ME" /> | The structure was based on the mitochondrial aldehyde dehydrogenase type two. RalDH2 in a monomer made up of 3 domains: a nucleotide-binding domain (1-136, 161-270), a catalytic domain (271-484), and a tetramerization domain (137-160, 485-484) as shown in [[Figure 1]].<ref name="Lamb AL, Newcomber ME" /> | ||
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===Cys-302=== | ===Cys-302=== | ||
In [[Figure 3]] it is possible to see the active site, which is where the substrate interacts with Cys-302. The Cys-302 residue acts as a nucleophilic active site on each domain as a hydrogen-bond turn that is enclosed deep inside the substrate access channel. This is where the large substrate molecules can gain access to the catalytic Cys-302. The side chain of Cys-302 is the nucleophile that attaches to the substrate retinol (at its carbonyl) when it is deprotonated. To get Cys-302 deprotonated, the amino acid Glu-268 is needed as the proton acceptor.<ref name="Structure of betaine aldehyde dehydrogenase at 2.1 A resolution">PMID:9792097 </ref> <ref name="The crystal structure of ternary complex of betaine aldehyde dehydrogenase">PMID:19013472 </ref> The amine backbone of Glu-268 helps stabilize the negatively charged transition state, which helps the enzyme result in an energetically favorable conformation. Asn-187 is also used as a transition site stabilizer and is on all four domains.<ref name="Structure of betaine aldehyde dehydrogenase at 2.1 A resolution">PMID:9792097 </ref> <ref name="The crystal structure of ternary complex of betaine aldehyde dehydrogenase">PMID:19013472 </ref> It | In [[Figure 3]] it is possible to see the active site, which is where the substrate interacts with Cys-302. The Cys-302 residue, highlighted in yellow in [[Figure 4]], acts as a nucleophilic active site on each domain as a hydrogen-bond turn that is enclosed deep inside the substrate access channel. This is where the large substrate molecules can gain access to the catalytic Cys-302. The side chain of Cys-302 is the nucleophile that attaches to the substrate retinol (at its carbonyl) when it is deprotonated. To get Cys-302 deprotonated, the amino acid Glu-268, highlighted in green in [[Figure 4]], is needed as the proton acceptor.<ref name="Structure of betaine aldehyde dehydrogenase at 2.1 A resolution">PMID:9792097 </ref> <ref name="The crystal structure of ternary complex of betaine aldehyde dehydrogenase">PMID:19013472 </ref> The amine backbone of Glu-268 helps stabilize the negatively charged transition state, which helps the enzyme result in an energetically favorable conformation. Asn-187, highlighted in red in [[Figure 4]], is also used as a transition site stabilizer and is on all four domains.<ref name="Structure of betaine aldehyde dehydrogenase at 2.1 A resolution">PMID:9792097 </ref> <ref name="The crystal structure of ternary complex of betaine aldehyde dehydrogenase">PMID:19013472 </ref> It works in a similar fashion as Glu-268, in that Asn-187 amine backbone is used to stabilize the negatively charged transition state. <ref name="Structure of betaine aldehyde dehydrogenase at 2.1 A resolution">PMID:9792097 </ref> <ref name="The crystal structure of ternary complex of betaine aldehyde dehydrogenase">PMID:19013472 </ref> | ||
