The structure and function of human dipeptidyl peptidase IV, possessing a unique eight-bladed β-propeller fold

被引：84

作者：

Hiramatsu, H

Kyono, K

Higashiyama, Y

Fukushima, C

Shima, H

Sugiyama, S

Inaka, K

Yamamoto, A

Shimizu, R

机构：

[1] Tanabe Seiyaku Co Ltd, Discovery Res Lab, Osaka 5328505, Japan

[2] Maruwa Foods Co Ltd, Nara 6391123, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 302卷 / 04期

关键词：

serine protease; dipeptidyl peptidase IV; prolyl oligopeptidase; X-ray crystal structure; beta-propeller fold;

D O I：

10.1016/S0006-291X(03)00258-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Dipeptidyl peptidase IV (DPPIV) is a serine protease, a member of the prolyl oligopeptidase (POP) family, and has been implicated in several diseases. Therefore, the development of DPPIV selective inhibitors, which are able to control the biological function of DPPIV, is important. We determined the crystal structure of human DPPIV at 2.6 Angstrom resolution. The molecule consists of a unique eight-bladed beta-propeller domain in the N-terminal region and a serine protease domain in the C-terminal region. Also, the large "cave" structure, which is thought to control the access of the substrate, is found on the side of the beta-propeller fold. Comparison of the overall amino acid sequence between human DPPIV and POP shows low homology (12.9%). In this paper, we report the structure of human DPPIV, especially focusing on a unique eight-bladed beta-propeller domain. We also discuss the way for the access of the substrate to this domain. (C) 2003 Elsevier Science (USA). All rights reserved.

引用

页码：849 / 854

页数：6

共 26 条

[1] Binding to human dipeptidyl peptidase IV by adenosine deaminase and antibodies that inhibit ligand binding involves overlapping, discontinuous sites on a predicted β propeller domain [J].