A Short, Strong Hydrogen Bond in the Active Site of Human Carbonic Anhydrase II

被引：126

作者：

Avvaru, Balendu Sankara ^{[1
]}

Kim, Chae Un ^{[3
]}

Sippel, Katherine H. ^{[1
]}

Gruner, Sol M. ^{[3
,4
]}

Agbandje-McKenna, Mavis ^{[1
]}

Silverman, David N. ^{[1
,2
]}

McKenna, Robert ^{[1
]}

机构：

[1] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA

[2] Univ Florida, Coll Med, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA

[3] Cornell Univ, Cornell High Energy Synchrotron Source, Ithaca, NY 14853 USA

[4] Cornell Univ, Dept Phys, Ithaca, NY 14853 USA

来源：

BIOCHEMISTRY | 2010年 / 49卷 / 02期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

AMINO-ACID SUBSTITUTIONS; PROTON-TRANSFER; CATALYTIC MECHANISM; DYNAMICS; CRYSTAL; MODEL;

D O I：

10.1021/bi902007b

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：

The crystal structure of human carbonic anhydrase II (HCA II) obtained at 0.9 angstrom resolution reveals that a water molecule, termed deep water, Dw, and bound in a hydrophobic pocket of the active site forms a short, strong hydrogen bond with the zinc-bound solvent molecule, a conclusion based on the observed oxygen-oxygen distance of 2.45 angstrom. This water structure hits similarities with hydrated hydroxide found in crystals of certain inorganic complexes. The energy required to displace Dw contributes in significant part to the weak binding of CO2 in the enzyme-substrate complex, a weak binding that enhances k(cat) for the conversion of CO2 into bicarbonate. In addition, this short, strong hydrogen bond is expected to contribute to the low pK(a) of the zinc-bound water and to promote proton transfer in catalysis.

引用

页码：249 / 251

页数：3

共 28 条

[1] BIHYDROXIDE (H3O2-) ANION - VERY SHORT, SYMMETRIC HYDROGEN-BOND [J].

ABUDARI, K ;

RAYMOND, KN ;

FREYBERG, DP .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1979, 101 (13) :3688-3689

[2]

AVVARU BS, 2009, BIOCHEMISTRY UNPUB

[3] Carbonic anhydrase: Evolution of the zinc binding site by nature and by design [J].

Christianson, DW ;

Fierke, CA .

ACCOUNTS OF CHEMICAL RESEARCH, 1996, 29 (07) :331-339

[4]

Cleland WW, 2000, BIOCHEMISTRY-US, V39, P1580

[5] Is a "proton wire" concerted or stepwise? A model study of proton transfer in carbonic anhydrase [J].

Cui, Q ;

Karplus, M .

JOURNAL OF PHYSICAL CHEMISTRY B, 2003, 107 (04) :1071-1078

[6]

DeLano W.L., 2002, The PyMOL molecular graphics system

[7] Entrapment of Carbon Dioxide in the Active Site of Carbonic Anhydrase II [J].

Domsic, John F. ;

Avvaru, Balendu Sankara ;

Kim, Chae Un ;

Gruner, Sol M. ;

Agbandje-McKenna, Mavis ;

Silverman, David N. ;

Mckenna, Robert .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (45) :30766-30771

[8]

Fersht A., 1999, Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding

[9] Atomic crystal and molecular dynamics simulation structures of human carbonic anhydrase II: Insights into the proton transfer mechanism [J].

Fisher, S. Zoe ;

Maupin, C. Mark ;

Budayova-Spano, Monika ;

Govindasamy, Lakshmanan ;

Tu, Chingkuang ;

Agbandje-McKenna, Mavis ;

Silverman, David N. ;

Voth, Gregory A. ;

McKenna, Robert .

BIOCHEMISTRY, 2007, 46 (11) :2930-2937

[10] Speeding up proton transfer in a fast enzyme: Kinetic and crystallographic studies on the effect of hydrophobic amino acid substitutions in the active site of human carbonic anhydrase II [J].

Fisher, S. Zoe ;

Tu, Chingkuang ;

Bhatt, Deepa ;

Govindasamy, Lakshmanan ;

Agbandje-McKenna, Mavis ;

McKenna, Robert ;

Silverman, David N. .

BIOCHEMISTRY, 2007, 46 (12) :3803-3813

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