Image 1: The proposed<unk>  homodimer structure; N-terminal domains in blue, C-terminal domains in orange. Lid region blocking the active site is shown in dark blue. Triglyceride binds to the C-terminal domain and the lid region, inducing a conformation change in<unk>  to make the active site accessible. The active site of<unk>  is composed of the conserved Ser-132, Asp-156, and His-241 triad. Other important regions of the N-terminal domain for catalysis includes an oxyanion hole (Trp-55, Leu-133), a lid region (residues 216-239), as well as a β5 loop (residues 54-64). The ApoC-II binding site is currently unknown, but it is predicted that residues on both N-and C-terminal domains are necessary for this interaction to occur. The C-terminal domain appears to confer<unk> ’s substrate specificity; it has a higher affinity for large triacylglyceride-rich lipoproteins than cholesterol-rich lipoproteins. The C-terminal domain is also important for binding to LDL’s receptors. Both the N-and C-terminal domains contain heparin binding sites distal to the lipid binding sites;<unk>  therefore serves as a bridge between the cell surface and lipoproteins. Importantly,<unk>  binding to the cell surface or receptors is not dependent on its catalytic activity. The<unk>  non-covalent homodimer has a head-to-tail arrangement of the monomers. The Ser/Asp/His triad is in a hydrophobic groove that is blocked from solvent by the lid. Upon binding to ApoC-II and lipid in the lipoprotein, the C-terminal domain presents the lipid substrate to the lid region. The lipid interacts with both the lid region and the hydrophobic groove at the active site; this causes the lid to move, providing access to the active site. The β5 loop folds back into the protein core, bringing one of the electrophiles of the oxyanion hole into position for lipolysis. The glycerol backbone of the lipid is then able to enter the active site and is hydrolyzed. Two molecules of ApoC-II can attach to each<unk>  dimer.> It is estimated that up to forty<unk>  dimers may act simultaneously on a single lipoprotein. In regard to kinetics, it is believed that release of product into circulation is the rate-limiting step in the reaction.
Lipoprotein lipase
Apolipoprotein
Lipoprotein-X
Heart-type fatty acid binding protein
Pancreatic elastase
VLDL receptor
Alpha-amylase
LDL receptor