Theoretical study revealing the functioning of a novel combination of catalytic motifs in histone deacetylase

被引：44

作者：

Vanommeslaeghe, K

De Proft, F

Loverix, S

Tourwé, D

Geerlings, P

机构：

[1] Free Univ Brussels, Gen Chem Grp, B-1050 Brussels, Belgium

[2] Free Univ Brussels, Organ Chem Grp ORGC, B-1050 Brussels, Belgium

[3] Vlaams Interuniv Inst Biotechnol, Dept Mol & Cellular Interact, B-1050 Brussels, Belgium

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 12期

关键词：

histone deacetylase; enzyme catalysis; density functional theory; protonation state;

D O I：

10.1016/j.bmc.2005.04.001

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：

Histone deacetylases (HDACs) have recently attracted considerable interest as targets in the treatment of cell proliferative diseases such as cancer. In the present work, the chemical properties of the active site of HDAC were theoretically investigated at a high computational level. Evidence was gathered for a novel catalytic mechanism, which differs from a previous proposal in the native protonation state of the His-Asp dyads, and in the deprotonation of water as a distinct step in the mechanism. (c) 2005 Elsevier Ltd. All rights reserved.

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收藏

页码：3987 / 3992

页数：6

相关论文

共 33 条

[1] Recent applications of density functional theory calculations to biomolecules [J].

Ban, FQ ;

Rankin, KN ;

Gauld, JW ;

Boyd, RJ .

THEORETICAL CHEMISTRY ACCOUNTS, 2002, 108 (01) :1-11

[2] The Protein Data Bank [J].

Berman, HM ;

Westbrook, J ;

Feng, Z ;

Gilliland, G ;

Bhat, TN ;

Weissig, H ;

Shindyalov, IN ;

Bourne, PE .

NUCLEIC ACIDS RESEARCH, 2000, 28 (01) :235-242

[3] CALCULATION OF SMALL MOLECULAR INTERACTIONS BY DIFFERENCES OF SEPARATE TOTAL ENERGIES - SOME PROCEDURES WITH REDUCED ERRORS [J].

BOYS, SF ;

BERNARDI, F .

MOLECULAR PHYSICS, 1970, 19 (04) :553-&

[4] Low-barrier hydrogen bonds and enzymatic catalysis [J].

Cleland, WW .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2000, 382 (01) :1-5

[5] The active site of a zinc-dependent metalloproteinase influences the computed pKa of ligands coordinated to the catalytic zinc ion [J].

Cross, JB ;

Duca, JS ;

Kaminski, JJ ;

Madison, VS .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (37) :11004-11007

[6] Histone deacetylases (HDACs): characterization of the classical HDAC family [J].

De Ruijter, AJM ;

Van Gennip, AH ;

Caron, HN ;

Kemp, S ;

Van Kuilenburg, ABP .

BIOCHEMICAL JOURNAL, 2003, 370 :737-749

[7] Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors [J].

Finnin M.S. ;

Donigian J.R. ;

Cohen A. ;

Richon V.M. ;

Rifkind R.A. ;

Marks P.A. ;

Breslow R. ;

Pavletich N.P. .

Nature, 1999, 401 (6749) :188-193

[8] Solvent effects .5. Influence of cavity shape, truncation of electrostatics, and electron correlation ab initio reaction field calculations [J].

Foresman, JB ;

Keith, TA ;

Wiberg, KB ;

Snoonian, J ;

Frisch, MJ .

JOURNAL OF PHYSICAL CHEMISTRY, 1996, 100 (40) :16098-16104

[9] Strong hydrogen bonding in chymotrypsin and other serine proteases [J].

Frey, PA .

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, 2004, 17 (6-7) :511-520

[10]

Frisch M.J., 2004, Gaussian 03

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