Jake Ezell Sandbox 2: Difference between revisions
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== | ==Malate Dehydrogenase== | ||
Malate Dehydrogenase (MDH)(PDB entry [http://www.pdb.org/pdb/explore/explore.do?structureId=2X0I 2x0i]) is most known for its role in the metabolic pathway in the tricarboxylic acid cycle[http://en.wikipedia.org/wiki/Citric_acid_cycle]; however, the enzyme is also in many other metabolic pathways such as glyoxylate bypass, amino acid synthesis, glucogenesis, and oxidation/reduction balance <ref>PMID:12537350</ref>. It is classified as a oxidoreductase[http://en.wikipedia.org/wiki/Oxidoreductase]. Malate Dehydrogenase has been extensively studied due to its many isozymes<ref>PMID:20173310</ref>. The enzyme exists in two places inside a cell, in the mitochondria and cytoplasm. In the mitochondria, the enzyme catalyzes the reaction of malate to oxaloacetate; but in the cytoplasm, the enzyme catalyzes oxaloacetate to malate to allow transport <ref>PMID:20173310</ref>. This conversion is an essential catalytic step in each different metabolic mechanism. The enzyme malate dehydrogenase is composed of either a dimer or tetramer <ref>PMID: 9834842<ref/>. During catalysis, the enzyme subunits are non-cooperative between active sites. The mitochondrial MDH is allosterically controlled by citrate, but no other known metabolic regulation mechanisms have been discovered. | Malate Dehydrogenase (MDH)(PDB entry [http://www.pdb.org/pdb/explore/explore.do?structureId=2X0I 2x0i]) is most known for its role in the metabolic pathway in the tricarboxylic acid cycle[http://en.wikipedia.org/wiki/Citric_acid_cycle]; however, the enzyme is also in many other metabolic pathways such as glyoxylate bypass, amino acid synthesis, glucogenesis, and oxidation/reduction balance <ref>PMID:12537350</ref>. It is classified as a oxidoreductase[http://en.wikipedia.org/wiki/Oxidoreductase]. Malate Dehydrogenase has been extensively studied due to its many isozymes<ref>PMID:20173310</ref>. The enzyme exists in two places inside a cell, in the mitochondria and cytoplasm. In the mitochondria, the enzyme catalyzes the reaction of malate to oxaloacetate; but in the cytoplasm, the enzyme catalyzes oxaloacetate to malate to allow transport <ref>PMID:20173310</ref>. This conversion is an essential catalytic step in each different metabolic mechanism. The enzyme malate dehydrogenase is composed of either a dimer or tetramer <ref>PMID: 9834842<ref/>. During catalysis, the enzyme subunits are non-cooperative between active sites. The mitochondrial MDH is allosterically controlled by citrate, but no other known metabolic regulation mechanisms have been discovered. | ||
The secondary structure of a single subunit contains a <scene name='Malate_dehydrogenase/Beta_sheeting_backbone/1'>9 beta sheet parallel backbone</scene> wrapped by <scene name='Malate_dehydrogenase/Alpha_wrapping_betas/1'>9 large alpha helices</scene>. Near the sodium bound end, 4 small anti-parallel beta sheets and 1 small alpha helix enable a turn in the residue chain<scene name='Malate_dehydrogenase/Small_turn/1'>(small turn)</scene>. Opposite the sodium bound ligand, 6 alpha helices point towards a common point, three on each side of the beta sheet backbone. The alpha helices form a <scene name='Jake_Ezell_Sandbox_2/Small_groove_nad/1'>small groove</scene> for a NAD+ cofactor to attach near the beta sheeting. The structure most nearly resembles an alternating alpha/beta classification. As for the 3D structure, the enzyme forms a sort of | The secondary structure of a single subunit contains a <scene name='Malate_dehydrogenase/Beta_sheeting_backbone/1'>9 beta sheet parallel backbone</scene> wrapped by <scene name='Malate_dehydrogenase/Alpha_wrapping_betas/1'>9 large alpha helices</scene>. Near the sodium bound end, 4 small anti-parallel beta sheets and 1 small alpha helix enable a turn in the residue chain<scene name='Malate_dehydrogenase/Small_turn/1'>(small turn)</scene>. Opposite the sodium bound ligand, 6 alpha helices point towards a common point, three on each side of the beta sheet backbone. The alpha helices form a <scene name='Jake_Ezell_Sandbox_2/Small_groove_nad/1'>small groove</scene> for a NAD+ cofactor to attach near the beta sheeting. The structure most nearly resembles an alternating alpha/beta classification. As for the 3D structure, the enzyme forms a sort of | ||
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[[Image:Malate_Dehydrogenase_Active_Site.JPG|250 px]] When this occurs, the other residues in the active site are brought closer to the substrate to enable the conversion. R102 and R109 are involved in this loop flip and thus invariant. After the loop flip, the malate complex is stabilized via hydrogen bonding before accepting a proton transfer from NADH to form oxaloacetate <ref>PMID:7849603</ref>. | [[Image:Malate_Dehydrogenase_Active_Site.JPG|250 px]] When this occurs, the other residues in the active site are brought closer to the substrate to enable the conversion. R102 and R109 are involved in this loop flip and thus invariant. After the loop flip, the malate complex is stabilized via hydrogen bonding before accepting a proton transfer from NADH to form oxaloacetate <ref>PMID:7849603</ref>. | ||
The evolutionary past of MDH shows a divergence to form lactate dehydrogenase (LDH) which functions in a very similar way to MDH. Although there is a very low sequence conservation among MDH and LDH’s [http://blast.ncbi.nlm.nih.gov/Blast.cgi] the structure of the enzyme has remained relatively conserved. The key difference between the two is in the | The evolutionary past of MDH shows a divergence to form lactate dehydrogenase (LDH) which functions in a very similar way to MDH. Although there is a very low sequence conservation among MDH and LDH’s [http://blast.ncbi.nlm.nih.gov/Blast.cgi] the structure of the enzyme has remained relatively conserved. The key difference between the two is in the substrate: LDH catalyzes pyruvate to lactate. | ||
{{STRUCTURE_2x0i | PDB=2x0i | SCENE= }} | |||
==References== | ==References== | ||
<references /> | <references /> | ||