Biosynthesis of cholesterol: Difference between revisions

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Alexander Berchansky

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 <scene name='92/929923/Cv/2'>3-hydroxy-3-methylglutaryl CoA (HMG-CoA)</scene> => <scene name='92/929923/Cv/3'>mevalonate</scene>
-The HMG binding pocket is the site of catalysis in HMGR. <scene name='HMG-CoA_Reductase/1dqa_cis_loop2/2'> The “cis-loop” that bends over the top of HMG </scene> ([[1dqa]]) is a critical structural element of this binding site. Residues <scene name='HMG-CoA_Reductase/1dqa_e_and_d/2'>E559 and D767</scene> and are positioned in the active site as is <scene name='HMG-CoA_Reductase/1dqa_k691/2'>K691 which is only 2.7 angstroms from the HMG O2 carbonyl oxygen</scene>. It is this K691 that likely stabilizes the negatively charged oxygen of the first mevaldyl-CoA intermediate.<ref name="Roitelman"/> The mevaldyl CoA intermediate is subsequently converted to Mavaldehyde with added stabilization from <scene name='HMG-CoA_Reductase/1dqa_h866/2'>H866, which is within hydrogen bonding distance of the thiol group</scene>.  It is then believed that the close proximity of <scene name='HMG-CoA_Reductase/1dqa_e_and_d/2'>E559 and D767</scene> increases the pKA of E559, allowing it to be a proton donor for the reduction of mevaldehyde into mevalonate.
+The HMG binding pocket is the site of catalysis in HMGR. <scene name='HMG-CoA_Reductase/1dqa_cis_loop2/2'> The “cis-loop” that bends over the top of HMG </scene> ([[1dqa]]) is a critical structural element of this binding site. Residues <scene name='HMG-CoA_Reductase/1dqa_e_and_d/2'>E559 and D767</scene> and are positioned in the active site as is <scene name='HMG-CoA_Reductase/1dqa_k691/2'>K691 which is only 2.7 angstroms from the HMG O2 carbonyl oxygen</scene>. It is this K691 that likely stabilizes the negatively charged oxygen of the first mevaldyl-CoA intermediate. The mevaldyl CoA intermediate is subsequently converted to Mavaldehyde with added stabilization from <scene name='HMG-CoA_Reductase/1dqa_h866/2'>H866, which is within hydrogen bonding distance of the thiol group</scene>.  It is then believed that the close proximity of <scene name='HMG-CoA_Reductase/1dqa_e_and_d/2'>E559 and D767</scene> increases the pKA of E559, allowing it to be a proton donor for the reduction of mevaldehyde into mevalonate.
 ''Mevalonate kinase''