Crystal structures of the Apo and Holo form of rat catechol-O-methyltransferase

被引：18

作者：

Tsuji, Eiichi ^{[1
]}

Okazaki, Kosuke ^{[1
]}

Isaji, Masayuki ^{[1
]}

Takeda, Kei ^{[2
]}

机构：

[1] R&D Kissei Pharmaceut Co Ltd, Mol Design Res, Azumino City, Nagano 3998304, Japan

[2] Grad Sch Biomed Sci, Dept Synthet Organ Chem, Minami Ku, Hiroshima 7348553, Japan

来源：

JOURNAL OF STRUCTURAL BIOLOGY | 2009年 / 165卷 / 03期

关键词：

Apo form; Holo form; Catechol-O-methyltransferase; X-ray crystal structure; BISUBSTRATE INHIBITORS; ENZYME; COMT; PURIFICATION; KINETICS;

D O I：

10.1016/j.jsb.2008.11.012

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：

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is a monomeric enzyme that catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (AdoMet) to the phenolic oxygen of substituted catechols. Although the inhibitor recognition pattern and AdoMet site have already been studied crystallographically, structural information on the catalytic cycle of COMT has not yet been obtained. In this study, comparison of the co-factor and inhibitor-bound structures revealed that the Apo form of COMT shows a conformational change and there was no cleft corresponding to the AdoMet-binding site; the overall structure was partially open form and the substrate recognition site was not clearly defined. The Holo form of COMT was similar to the quaternary structure except for the beta 6-beta 7 and alpha 2-alpha 3 ligand recognition loops. These conformational changes provide a deeper insight into the structural events occurring in reactions catalyzed by AdoMet. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：133 / 139

页数：7

共 32 条

[1]

[Anonymous], 1992, JOINT CCP4 ESF EAMCB

[2] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].

BAILEY, S .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763

[3] Kinetics and crystal structure of catechol-O-methyltransferase complex with co-substrate and a novel inhibitor with potential therapeutic application [J].

Bonifácio, MJ ;

Archer, M ;

Rodrigues, ML ;

Matias, PM ;

Learmonth, DA ;

Carrondo, MA ;

Soares-da-Silva, P .

MOLECULAR PHARMACOLOGY, 2002, 62 (04) :795-805

[4] Molecular dynamics simulations of the enzyme Catechol-O-Methyltransferase:: methodological issues [J].

Bunker, A. ;

Mannisto, P. T. ;

Pierre, J. -F. St. ;

Rog, T. ;

Pomorski, P. ;

Stimson, L. ;

Karttunen, M. .

SAR AND QSAR IN ENVIRONMENTAL RESEARCH, 2008, 19 (1-2) :179-189

[5]

EDMOND YL, 2000, J AM CHEM SOC, V122, P7165

[6]

EDMOND YL, 1998, J AM CHEM SOC, V120, P12387

[7]

GULDBERG HC, 1975, PHARMACOL REV, V27, P135

[8] EFFECT OF A NOVEL CATECHOL-O-METHYLTRANSFERASE INHIBITOR, NITECAPONE, ON THE METABOLISM OF L-DOPA IN HEALTHY-VOLUNTEERS [J].

KAAKKOLA, S ;

GORDIN, A ;

JARVINEN, M ;

WIKBERG, T ;

SCHULTZ, E ;

NISSINEN, E ;

PENTIKAINEN, PJ ;

RITA, H .

CLINICAL NEUROPHARMACOLOGY, 1990, 13 (05) :436-447

[9] DISTRIBUTION OF CATECHOL-O-METHYLTRANSFERASE ENZYME IN RAT-TISSUES [J].

KARHUNEN, T ;

TILGMANN, C ;

ULMANEN, I ;

JULKUNEN, I ;

PANULA, P .

JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1994, 42 (08) :1079-1090

[10] Molecular mechanisms controlling the rate and specificity of catechol O-methylation by human soluble catechol O-methyltransferase [J].

Lautala, P ;

Ulmanen, I ;

Taskinen, J .

MOLECULAR PHARMACOLOGY, 2001, 59 (02) :393-402

← 1 2 3 4 →