1NU6

Crystal structure of human Dipeptidyl Peptidase IV (DPP-IV)

Summary for 1NU6

• Entry DOI: 10.2210/pdb1nu6/pdb
• Related: 1NU8
• Descriptor: Dipeptidyl peptidase IV, 2-acetamido-2-deoxy-beta-D-glucopyranose, MERCURY (II) ION, ... (4 entities in total)
• Functional Keywords: exopeptidase, beta barrel, alpha/beta hydrolase fold, dpp-iv, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 171898.44

Authors

Hennig, M.,Stihle, M.,Thoma, R.,Ruf, A. (deposition date: 2003-01-31, release date: 2003-08-26, Last modification date: 2024-11-13)

Primary citation

Thoma, R.,Loeffler, B.,Stihle, M.,Huber, W.,Ruf, A.,Hennig, M.
Structural Basis of Proline-Specific Exopeptidase Activity as Observed in Human Dipeptidyl Peptidase-IV.
Structure, 11:947-959, 2003

PubMed Abstract: Inhibition of dipeptidyl peptidase IV (DPP-IV), the main glucagon-like peptide 1 (GLP1)-degrading enzyme, has been proposed for the treatment of type II diabetes. We expressed and purified the ectodomain of human DPP-IV in Pichia pastoris and determined the X-ray structure at 2.1 A resolution. The enzyme consists of two domains, the catalytic domain, with an alpha/beta hydrolase fold, and a beta propeller domain with an 8-fold repeat of a four-strand beta sheet motif. The beta propeller domain contributes two important functions to the molecule that have not been reported for such structures, an extra beta sheet motif that forms part of the dimerization interface and an additional short helix with a double Glu sequence motif. The Glu motif provides recognition and a binding site for the N terminus of the substrates, as revealed by the complex structure with diprotin A, a substrate with low turnover that is trapped in the tetrahedral intermediate of the reaction in the crystal.

PubMed: 12906826
DOI: 10.1016/S0969-2126(03)00160-6

Experimental method

X-RAY DIFFRACTION (2.1 Å)