Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an enzyme of the glycolysis pathway. It catalyzes the synthesis of 1,3-bisphosphoglycerate, a "high energy" intermediate used for the synthesis of ATP.
   We will observe structural features of this enzyme at many levels: subunit interactions; domain composition of subunits; secondary structure, and substrate binding.

Subunit Structure

   The complete enzyme is a tetramer. Each of the four identical subunits occupies the vertex of a tetrahedron.
Subunit 1
Subunit 2
Subunit 3
Subunit 4

Domain Structure

   We will now concentrate on the structure of subunit 1. When we look at the path of the backbone of the protein we see that it makes two "spaghetti tangles." Each of these tangles is a domain. Frequently one domain of a protein is responsible for carrying out one task in the function of the protein. In the case of GAPDH one domain principally binds NAD+ while the other binds glyceraldehyde 3-phospate (GAP).

Zoom to Subunit 1  
NAD+ binding domain
GAP binding domain

   Use the above table to select and restrict the two domains. View them in different display modes. Locate the N- and C-terminus of each domain.


Trace the backbone through each domain. Observe that the amino acid residues in each domain interact predominantly with other amino acid residues within the same domain by displaying in a mode such as "Ball & Stick" or "Spacfill."

Ligand binding


Secondary Structure within Domains

   Protein domains are comprised of central alpha helices and beta sheets connected by loops.
NAD+ domain
Alpha helix   side chains
  one turn of helix   side chains
Beta sheet   side chains
  single strand   side chains
Beta hairpin   side chains
Hydrogen Bonds