Active site analysis of 17β-hydroxysteroid dehydrogenase type 1 enzyme complexes with SPROUT

被引：12

作者：

Alho-Richmond, S ^{[1
]}

Lilienkampf, A ^{[1
]}

Wähälä, K ^{[1
]}

机构：

[1] Univ Helsinki, Dept Chem, Organ Chem Lab, FIN-00014 Helsinki, Finland

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2006年 / 248卷 / 1-2期

关键词：

17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD1); breast cancer; de novo ligand design; SPROUT;

D O I：

10.1016/j.mce.2005.12.004

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Estrogens, especially estradiol, hive been shown to stimulate the proliferation of hormone-dependent types of breast cancer cells. 17 beta-Hydroxysteroid dehydrogenase type 1 (17 beta-HSDl) enzyme catalyses the synthesis of the active female estrogen, estradiol and is thus an attractive target for structure-based ligand design for the prevention and control of breast tumour growth. In this study, the active site of 17 beta-HSDl has been reviewed, and three crystal structure omplexes (estradiol/NADP(+), equilin/NADP(+), dehydroepiandrosterone) of 17 beta-HSDl have been selected to be analysed for de novo ligand design. The boundary surface, hydrophobic interactions and hydrogen bonding sites in the ligand binding domain for each ligand complex were analysed to create a comprehensive image of the active site. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

引用

页码：208 / 213

页数：6

共 22 条

[1]

ALHO S, 2005, THESIS U HELSINKI GU

[2] Crystal structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase complexed with 17 beta-estradiol [J].

Azzi, A ;

Rehse, PH ;

Zhu, DW ;

Campbell, RL ;

Labrie, F ;

Lin, SX .

NATURE STRUCTURAL BIOLOGY, 1996, 3 (08) :665-668

[3] The structure of a complex of human 17 beta-hydroxysteroid dehydrogenase with estradiol and NADP(+) identifies two principal targets for the design of inhibitors [J].

Breton, R ;

Housset, D ;

Mazza, C ;

FontecillaCamps, JC .

STRUCTURE, 1996, 4 (08) :905-915

[4] Pseudo-symmetry of C19-steroids, alternative binding orientations and multispecificity in human estrogenic 17β-hydroxysteroid dehydrogenase [J].

Gangloff, A ;

Shi, R ;

Nahoum, V ;

Lin, SX .

FASEB JOURNAL, 2002, 16 (14) :274-+

[5] STRUCTURE OF HUMAN ESTROGENIC 17-BETA-HYDROXYSTEROID DEHYDROGENASE AT 2.20 ANGSTROM RESOLUTION [J].

GHOSH, D ;

PLETNEV, VZ ;

ZHU, DW ;

WAWRZAK, Z ;

DUAX, WL ;

PANGBORN, W ;

LABRIE, F ;

LIN, SX .

STRUCTURE, 1995, 3 (05) :503-513

[6] Amplification of HSD17B1 and ERBB2 in primary breast cancer [J].

Gunnarsson, C ;

Ahnström, M ;

Kirschner, K ;

Olsson, B ;

Nordenskjöld, B ;

Rutqvist, LE ;

Skoog, L ;

Stål, O .

ONCOGENE, 2003, 22 (01) :34-40

[7] Dehydroepiandrosterone and dihydrotestosterone recognition by human estrogenic 17β-hydroxysteroid dehydrogenase -: C-18/C-19 steroid discrimination and enzyme-induced strain [J].

Han, Q ;

Campbell, RL ;

Gangloff, A ;

Huang, YW ;

Lin, SX .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (02) :1105-1111

[8]

HIRVELA L, 2005, Patent No. 2005032527

[9] Validation of the SPROUT de novo design program [J].

Law, JMS ;

Fung, DYK ;

Zsoldos, Z ;

Simon, A ;

Szabo, Z ;

Csizmadia, IG ;

Johnson, AP .

JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 2003, 666 :651-657

[10]

LILIENKAMPF A, 2001, KEMIA KEMI, V7, P542

← 1 2 3 →