Residues determining the binding specificity of uncompetitive inhibitors to tissue-nonspecific alkaline phosphatase

被引：75

作者：

Kozlenkov, A

Le Du, MH

Cuniasse, P

Ny, T

Hoylaerts, MF

Millán, JL

机构：

[1] Umea Univ, Dept Med Biosci, Umea, Sweden

[2] Dept Ingn & Etudes Prot, Gif Sur Yvette, France

[3] Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden

[4] Katholieke Univ Leuven, Ctr Mol & Vasc Biol, Louvain, Belgium

[5] Burnham Inst, La Jolla, CA 92037 USA

来源：

JOURNAL OF BONE AND MINERAL RESEARCH | 2004年 / 19卷 / 11期

关键词：

alkaline phosphatase; enzyme kinetics; site-directed mutagenesis; computer modeling; soft tissue ossification; therapeutic inhibitors; drug design;

D O I：

10.1359/JBMR.040608

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Recent data have pointed to TNALP as a therapeutic target for soft-tissue ossification abnormalities. Here, we used mutagenesis, kinetic analysis, and computer modeling to identify the residues important for the binding of known ALP inhibitors to the TNALP active site. These data will enable drug design efforts aimed at developing improved specific TNALP inhibitors for therapeutic use.

引用

页码：1862 / 1872

页数：11

共 57 条

[1]

ALI SY, 1971, BIOCHEM J, V122, pP56

[2] ISOLATION AND CHARACTERIZATION OF CALCIFYING MATRIX VESICLES FROM EPIPHYSEAL CARTILAGE [J].