The acylation mechanism of CTX-M β-lactamase at 0.88 Å resolution

被引：57

作者：

Chen, Yu

Bonnet, Richard

Shoichet, Brian K.

机构：

[1] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA

[2] Ctr Hosp Univ, Fac Med, Bacteriol Lab, F-63001 Clermont Ferrand, France

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2007年 / 129卷 / 17期

关键词：

D O I：

10.1021/ja0712064

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The apo crystal structure of CTX-M-9 beta-lactamase has been determined to 0.88 A at pH 8.8. This unusually clear picture of proton positions and residue interactions supports the role of Glu166 as the general base for the controversial acylation step of class A beta-lactamase catalysis. The ability to distinguish low-energy conformations sampled by the enzyme allows us to link the two conformations of Lys73 to different protonation states of Glu166.

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页码：5378 / +

页数：4

相关论文

共 25 条

[1]

ADACHI H, 1991, J BIOL CHEM, V266, P3186

[2] Protonation of the β-lactam nitrogen is the trigger event in the catalytic action of class A β-lactamases [J].

Atanasov, BP ;

Mustafi, D ;

Makinen, MW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (07) :3160-3165

[3] Growing group of extended-spectrum β-lactamases:: The CTX-M enzymes [J].

Bonnet, R .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2004, 48 (01) :1-14

[4] Structure, function, and inhibition along the reaction coordinate of CTX-M β-lactamases [J].

Chen, Y ;

Shoichet, B ;

Bonnet, R .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (15) :5423-5434

[5] Atomic resolution structures of CTX-M β-lactamases:: Extended spectrum activities from increased mobility and decreased stability [J].

Chen, Y ;

Delmas, J ;

Sirot, J ;

Shoichet, B ;

Bonnet, R .

JOURNAL OF MOLECULAR BIOLOGY, 2005, 348 (02) :349-362

[6] The catalytic mechanism of beta-lactamases: NMR titration of an active-site lysine residue of the TEM-1 enzyme [J].

Damblon, C ;

Raquet, X ;

Lian, LY ;

LamotteBrasseur, J ;

Fonze, E ;

Charlier, P ;

Roberts, GCK ;

Frere, JM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (05) :1747-1752

[7] LEAST-SQUARES REFINEMENT AND WEIGHTED DIFFERENCE SYNTHESIS [J].

DUNITZ, JD ;

SEILER, P .

ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE CRYSTAL ENGINEERING AND MATERIALS, 1973, 29 (MAR15) :589-595

[8] SITE-DIRECTED MUTAGENESIS OF GLUTAMATE-166 IN BETA-LACTAMASE LEADS TO A BRANCHED PATH MECHANISM [J].

ESCOBAR, WA ;

TAN, AK ;

LEWIS, ER ;

FINK, AL .

BIOCHEMISTRY, 1994, 33 (24) :7619-7626

[9] SITE-DIRECTED MUTAGENESIS OF BETA-LACTAMASE-I - SINGLE AND DOUBLE MUTANTS OF GLU-166 AND LYS-73 [J].

GIBSON, RM ;

CHRISTENSEN, H ;

WALEY, SG .

BIOCHEMICAL JOURNAL, 1990, 272 (03) :613-619

[10] The importance of a critical protonation state and the fate of the catalytic steps in class A β-lactamases and penicillin-binding proteins [J].

Golemi-Kotra, D ;

Meroueh, SO ;

Kim, C ;

Vakulenko, SB ;

Bulychev, A ;

Stemmler, AJ ;

Stemmler, TL ;

Mobashery, S .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (33) :34665-34673