PDB file 1DQA
Structure of the catalytic portion of human HMG-CoA Reductase. Structure determined by E. S. Istvan, M. Palnitkar, S. K. Buchanan, & J. Deisenhofer in 1999.
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The catalytic domain of the enzyme, when cleaved off of the membrane domain, assembles into a tetramer, consisting of two dimers. The enzyme has been crystallized with CoA and hydroxymethylglutarate (HMG) at the active site, instead of the natural substrate HMG-CoA.
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There are four active site complexes in this tetrameric form of the catalytic domain.
Zoom in to view CoA, NADP+, & HMG (hydroxymethylglutarate) at the active site.
Identify the positions of functional groups of the two coenzymes relative to HMG.
In particular, note the position of the nicotinamide ring of NADP+ relative to the carboxyl of HMG-CoA that would be reduced by NADPH.
and change its display. This residue's hydroxyl group is phosphorylated by AMP-Dependent Protein Kinase, leading to
Question: Is this regulatory site at the active site?
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Where are the active sites located?
Would you expect a monomer of the enzyme to be catalytically active?
on Cholesterol Synthesis
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