Sandbox 55: Difference between revisions

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==HMG-CoA Reductase==

~~<applet load='1dq9' size='350' frame='true' align='right' caption='Catalytic portion of HMG-CoA Reductase in complex with its substrate, HMG-CoA' />~~

HMG-CoA is an endoplasmic reticulum transmembrane glycoprotein. It is a tetramer and an NADPH-dependent enzyme. HMG-CoA reductase contains an N-terminal membrane domain and a C-terminal catalytic domain. The catalytic portion can be further subdivided into an N-domain (N-terminal), a large L-domain, and a small S-domain. The L-domain binds the substrate, and the S-domain binds NADP<ref>"Pfam: Family: HMG-CoA_red (PF00368)." Pfam: Home Page. Web. 10 Mar. 2011. <http://pfam.sanger.ac.uk/family?acc=PF00368>.</ref>.

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The active sites of HMG-CoA reductase are located at the interface of the two monomers of a dimer. Each active site has a loop that folds over part of the binding pocket; the loop contains an unusual cis-peptide bond that is highly conserved. The loop folds over the active site when both substrates (HMG-CoA and NADPH) are bound to exclude solvent from the active site.

The <scene name='Sandbox_55/Four_active_sites_and_residues/1'>four active sites</scene> of HMG-CoA reductase are located at the interface of the two monomers of a dimer. Each active site has a loop that folds over part of the binding pocket; the loop contains an unusual cis-peptide bond that is highly conserved. The loop folds over the active site when both substrates (HMG-CoA and NADPH) are bound to exclude solvent from the active site.

The HMG binding pocket is the site of catalysis for HMG-CoA reductase. Three residues are essential for catalysis, E559, D767, and K691. K691 is positioned only 2.7 angstroms from the HMG O2 carbonyl oxygen, and stabilizes the negative charge of the first intermediate. H866 also stabilizes the thiol group. It is also believed that the closeness of E559 and D767 increases the pKa of E559, which allows it to be a proton donor for the final reduction of mevaldehyde to mevalonate.

Sandbox 55: Difference between revisions

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@@ Line 42: / Line 42: @@
 ==HMG-CoA Reductase==
-<applet load='1dq9' size='350' frame='true' align='right' caption='Catalytic portion of HMG-CoA Reductase in complex with its substrate, HMG-CoA' />
 HMG-CoA is an endoplasmic reticulum transmembrane glycoprotein. It is a tetramer and an NADPH-dependent enzyme. HMG-CoA reductase contains an N-terminal membrane domain and a C-terminal catalytic domain. The catalytic portion can be further subdivided into an N-domain (N-terminal), a large L-domain, and a small S-domain. The L-domain binds the substrate, and the S-domain binds NADP<ref>"Pfam: Family: HMG-CoA_red (PF00368)." Pfam: Home Page. Web. 10 Mar. 2011. <http://pfam.sanger.ac.uk/family?acc=PF00368>.</ref>.
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 <applet load='1hwk' size='350' frame='true' align='left' caption='HMG-CoA Reductase in complex with Lipitor' />
-The active sites of HMG-CoA reductase are located at the interface of the two monomers of a dimer. Each active site has a loop that folds over part of the binding pocket; the loop contains an unusual cis-peptide bond that is highly conserved. The loop folds over the active site when both substrates (HMG-CoA and NADPH) are bound to exclude solvent from the active site.
+The <scene name='Sandbox_55/Four_active_sites_and_residues/1'>four active sites</scene> of HMG-CoA reductase are located at the interface of the two monomers of a dimer. Each active site has a loop that folds over part of the binding pocket; the loop contains an unusual cis-peptide bond that is highly conserved. The loop folds over the active site when both substrates (HMG-CoA and NADPH) are bound to exclude solvent from the active site.
 The HMG binding pocket is the site of catalysis for HMG-CoA reductase. Three residues are essential for catalysis, E559, D767, and K691. K691 is positioned only 2.7 angstroms from the HMG O2 carbonyl oxygen, and stabilizes the negative charge of the first intermediate. H866 also stabilizes the thiol group. It is also believed that the closeness of E559 and D767 increases the pKa of E559, which allows it to be a proton donor for the final reduction of mevaldehyde to mevalonate.