Motion of the Zinc Ions in Catalysis by a Dizinc Metallo-β-Lactamase

被引：30

作者：

Breece, Robert M. ^{[2
]}

Hu, Zhenxin ^{[3
]}

Bennett, Brian ^{[1
]}

Crowder, Michael W. ^{[3
]}

Tierney, David L. ^{[2
,3
]}

机构：

[1] Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA

[2] Univ New Mexico, Dept Chem & Chem Biol, Albuquerque, NM 87131 USA

[3] Miami Univ, Dept Chem & Biochem, Oxford, OH 45056 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2009年 / 131卷 / 33期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

STENOTROPHOMONAS-MALTOPHILIA; REACTION INTERMEDIATE; L1; HYDROLYSIS; MECHANISM; ZN(II);

D O I：

10.1021/ja902534b

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We report rapid-freeze-quench X-ray absorption spectroscopy of a dizinc metallo-beta-lactamase (MBL) reaction intermediate. The Zn(II) ions in the dinuclear active site of the S. maltophilia Class B3 M beta L move away from each other, by similar to 0.3 angstrom after 10 ms of reaction with nitrocefin, from 3.4 to 3.7 angstrom. Together with our previous characterization of the resting enzyme and its nitrocefin product complex, where the Zn(II) ion separation relaxes to 3.6 angstrom, these data indicate a scissoring motion of the active site that accompanies the ring-opening step. The average Zn(II) coordination number of 4.5 in the resting enzyme appears to be maintained throughout the reaction with nitrocefin. This is the first direct structural information available on early stage dizinc metallo-beta-lactamase catalysis.

引用

页码：11642 / +

页数：3

共 15 条

[11] Antibiotic recognition by binuclear metallo-β-lactamases revealed by X-ray crystallography [J].

Spencer, J ;

Read, J ;

Sessions, RB ;

Howell, S ;

Blackburn, GM ;

Gamblin, SJ .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (41) :14439-14444

[12] The quorum-quenching lactonase from Bacillus thuringiensis is a metalloprotein [J].

Thomas, PW ;

Stone, EM ;

Costello, AL ;

Tierney, DL ;

Fast, W .

BIOCHEMISTRY, 2005, 44 (20) :7559-7569

[13] Trapping and Characterization of a Reaction Intermediate in Carbapenem Hydrolysis by B-cereus Metallo-β-lactamase [J].

Tioni, Mariana F. ;

Llarrull, Leticia I. ;

Poeylaut-Palena, Andres A. ;

Marti, Marcelo A. ;

Saggu, Miguel ;

Periyannan, Gopal R. ;

Mata, Ernesto G. ;

Bennett, Brian ;

Murgida, Daniel H. ;

Vila, Alejandro J. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (47) :15852-15863

[14] The crystal structure of the L1 metallo-β-lactamase from Stenotrophomonas maltophilia at 1.7 Å resolution [J].

Ullah, JH ;

Walsh, TR ;

Taylor, IA ;

Emery, DC ;

Verma, CS ;

Gamblin, SJ ;

Spencer, J .

JOURNAL OF MOLECULAR BIOLOGY, 1998, 284 (01) :125-136

[15] Antibiotic deactivation by a dizinc β-lactamase:: Mechanistic insights from QM/MM and DFT studies [J].

Xu, Dingguo ;

Guo, Hua ;

Cui, Qiang .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2007, 129 (35) :10814-10822

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