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

[1] Metallo-β-lactamases (classification, activity, genetic organization, structure, zinc coordination) and their superfamily [J].

Bebrone, Carine .

BIOCHEMICAL PHARMACOLOGY, 2007, 74 (12) :1686-1701

[2] Site-selective binding of Zn(II) to metallo-β-lactamase L1 from Stenotrophomonas maltophilia [J].

Costello, A ;

Periyannan, G ;

Yang, KW ;

Crowder, MW ;

Tierney, DL .

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, 2006, 11 (03) :351-358

[3] Metallo-β-lactamases:: does it take two to tango? [J].

Cricco, JA ;

Orellano, EG ;

Rasia, RM ;

Ceccarelli, EA ;

Vila, AJ .

COORDINATION CHEMISTRY REVIEWS, 1999, 190 :519-535

[4] Standard numbering scheme for class B β-lactamases [J].

Galleni, M ;

Lamotte-Brasseur, J ;

Rossolini, GM ;

Spencer, J ;

Dideberg, O ;

Frère, JM .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (03) :660-663

[5] Direct evidence that the reaction intermediate of metallo-β-lactamase L1 is metal bound [J].

Garrity, JD ;

Bennett, B ;

Crowder, MW .

BIOCHEMISTRY, 2005, 44 (03) :1078-1087

[6] Role of the Zn1 and Zn2 sites in Metallo-β-lactamase L1 [J].

Hu, Zhenxin ;

Periyannan, Gopalraj ;

Bennett, Brian ;

Crowder, Michael W. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (43) :14207-14216

[7] Intermediate in β-lactam hydrolysis catalyzed by a dinuclear zinc(II) complex:: Relevance to the mechanism of metallo-β-lactamase [J].

Kaminskaia, NV ;

Spingler, B ;

Lippard, SJ .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (27) :6555-6563

[8] Metal Content and Localization during Turnover in B-cereus Metallo-β-lactamase [J].

Llarrull, Leticia I. ;

Tioni, Mariana F. ;

Vila, Alejandro J. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (47) :15842-15851

[9] Kinetic mechanism of metallo-β-lactamase L1 from Stenotrophomonas maltophilia [J].

McManus-Munoz, S ;

Crowder, MW .

BIOCHEMISTRY, 1999, 38 (05) :1547-1553

[10] In vivo folding of recombinant metallo-β-lactamase L1 requires the presence of Zn(II) [J].

Periyannan, G ;

Shaw, PJ ;

Sigdel, T ;

Crowder, MW .

PROTEIN SCIENCE, 2004, 13 (08) :2236-2243

← 1 2 →