Crystal structures of human dipeptidyl peptidase IV in its apo and diprotin B-complexed forms.

Abstract:

:Dipeptidyl peptidase IV (DPPIV), which belongs to the prolyl oligopeptidase family of serine proteases, is known to have a variety of regulatory biological functions and has been shown to be implicated in type 2 diabetes. It is therefore important to develop selective human DPPIV (hDPPIV) inhibitors. In this study, we determined the crystal structure of apo hDPPIV at 1.9 A resolution. Our high-resolution crystal structure of apo hDPPIV revealed the presence of sodium ion and glycerol molecules at the active site. In order to elucidate the hDPPIV binding mode and substrate specificity, we determined the crystal structure of hDPPIV-diprotin B (Val-Pro-Leu) complex at 2.1 A resolution, and clarified the difference in binding mode between diprotin B and diprotin A (Ile-Pro-Ile) into the active site of hDPPIV. Comparison between our crystal structures and the reported apo hDPPIV structures revealed that positively charged functional groups and conserved water molecules contributed to the interaction of ligands with hDPPIV. These results are useful for the design of potent hDPPIV inhibitors.

authors

Hiramatsu H,Kyono K,Yamamoto A,Saeki K,Shima H,Sugiyama S,Inaka K,Shimizu R

doi

10.1111/j.1745-7270.2007.00289.x

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

335-43

issue

5

eissn

1672-9145

issn

1745-7270

journal_volume

39

pub_type

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