Biomedical Engineering Reference
In-Depth Information
Figure 5.1
Expression patterns of DPP-4, FAP, DPP-8, and DPP-9 (modified from
reference 1).
endothelium of all organs examined, including liver, spleen, lungs, and brain;
by acinar cells of mucous, salivary glands, and pancreas; and by immune
organs such as thymus, spleen, and lymph node (Figure 5.1).
21,41-44
Soluble
DPP-4 is found in serum, seminal fluid, saliva, kidney, liver, and bile, and has
been purified from serum, seminal fluid, kidney, and liver.
43,45-48
5.2.3 Structure of DPP-4
The crystal structure of DPP-4, [PDB code: 1N1M
49
or 1X70
50
] reveals a
topology composed of an N-terminal eight-blade b-propeller domain and a C-
terminal a/b-hydrolase domain. The a/b-hydrolase domain, which contains the
catalytic triad, is highly conserved throughout the DPP-4 protein family. The b-
propeller domain contains both internal residues of the catalytic pocket and
surface residues associated with extra-enzymatic functions, and is composed of
both conserved and highly variable regions. DPP-4 is enzymatically active as a
homodimer, and both domains provide residues that form the dimerization
interface and contribute parts of the catalytic pocket and substrate binding
site.
49,51
DPP-4 has a large internal cavity but can accommodate only a few N-
terminal residues of substrates within its active site. The active site is buried
deep within the protein and is formed by amino acids that include the catalytic
triad and both conserved and variable residues from each domain (Figure
5.2A). The conserved residues that form the active site in DPP-4 include the
