How β-Lactamases Have Driven Pharmaceutical Drug Discovery

A functional classification scheme for beta-lactamases and its correlation with molecular structure

1995 • 2,497 citations

The structure of β-lactamases

1980 • 1,705 citations

An Enzyme from Bacteria able to Destroy Penicillin

1940 • 1,283 citations

In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors

1995 • 984 citations

Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine.

1965 • 943 citations

Transferable resistance to cefotaxime, cefoxitin, cefamandole and cefuroxime in clinical isolates of Klebsiella pneumoniae and Serratia marcescens

1983 • 926 citations

The β-Lactamases of Gram-Negative Bacteria and their Possible Physiological Role

1973 • 719 citations

Clavulanic Acid: a Beta-Lactamase-Inhibiting Beta-Lactam from Streptomyces clavuligerus

1977 • 695 citations

SERINE β-LACTAMASES AND PENICILLIN-BINDING PROTEINS

1991 • 610 citations

Nosocomial Outbreak of Klebsiella Infection Resistant to Late-Generation Cephalosporins

1993 • 605 citations

Evolution and Dissemination of β-Lactamases Accelerated by Generations of β-Lactam Antibiotics

1997 • 589 citations

Penicillinase Synthesis Controlled By Infectious R Factors In Enterobacteriaceae

1965 • 555 citations

The β-lactamases of Gram-negative bacteria and their rôle in resistance to β-lactam antibiotics

1976 • 539 citations

Molecular structure of the acyl-enzyme intermediate in β-lactam hydrolysis at 1.7 Å resolution

1992 • 515 citations

Thienamycin, a new .BETA.-lactam antibiotic. I. Discovery, taxonomy, isolation and physical properties.

1979 • 502 citations

Extraction of a Highly Potent Penicillin Inactivator from Penicillin Resistant Staphylococci

1944 • 487 citations

The 3-D structure of a zinc metallo-beta-lactamase from Bacillus cereus reveals a new type of protein fold.

1995 • 449 citations

CP-45,899, a Beta-Lactamase Inhibitor That Extends the Antibacterial Spectrum of Beta-Lactams: Initial Bacteriological Characterization

1978 • 399 citations

Kinship and Diversification of Bacterial Penicillin-Binding Proteins and β-Lactamases

1998 • 399 citations

Naturally-occurring .BETA.-lactamase inhibitors with antibacterial activity.

1976 • 388 citations

ampC cephalosporinase of Escherichia coli K-12 has a different evolutionary origin from that of beta-lactamases of the penicillinase type.

1981 • 384 citations

Transferable resistance to third-generation cephalosporins in clinical isolates of Klebsiella pneumoniae: identification of CTX-1, a novel β-lactamase

1987 • 366 citations

Crystal structure of the wide-spectrum binuclear zinc β-lactamase from Bacteroides fragilis

1996 • 361 citations

Carbapenem-hydrolyzing beta-lactamases

1997 • 360 citations

Crystal structure of Escherichia coli TEM1 β‐lactamase at 1.8 Å resolution

1993 • 349 citations

Metabolism of Thienamycin and Related Carbapenem Antibiotics by the Renal Dipeptidase, Dehydropeptidase-I

1982 • 340 citations

Azthreonam (SQ 26,776), a synthetic monobactam specifically active against aerobic gram-negative bacteria

1982 • 326 citations

Rapid Development of Ciprofloxacin Resistance in Methicillin-Susceptible and -Resistant Staphylococcus aureus

1991 • 320 citations

Extended-spectrum and inhibitor-resistant TEM-type beta-lactamases: mutations, specificity, and three-dimensional structure

1995 • 313 citations

Thienamycin: development of imipenem-cilastatin

1983 • 305 citations

Characterization of beta-lactamases

1989 • 302 citations

Recent Developments in the Field of β‐Lactam Antibiotics

1985 • 297 citations

Carbapenems, a new class of beta-lactam antibiotics

1985 • 283 citations

Surveillance of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States in 1996–1997 respiratory season

1997 • 281 citations

Evolution of extended-spectrum beta-lactam resistance (SHV-8) in a strain of Escherichia coli during multiple episodes of bacteremia

1997 • 276 citations

Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: active efflux as a contributing factor to beta-lactam resistance

1994 • 274 citations

Kinetic interactions of tazobactam with beta-lactamases from all major structural classes

1993 • 273 citations

PENICILLIN AND CEPHALOSPORIN BIOSYNTHETIC GENES: Structure, Organization, Regulation, and Evolution

1992 • 260 citations

Penicillin-Sensitive Enzymes in Peptidoglycan Biosynthesis

1984 • 251 citations

Characterization of IMI-1 beta-lactamase, a class A carbapenem-hydrolyzing enzyme from Enterobacter cloacae

1996 • 212 citations

Kinetic studies on the inactivation of Escherichia coli RTEM β-lactamase by clavulanic acid

1978 • 204 citations

Evolution of an enzyme activity: crystallographic structure at 2-A resolution of cephalosporinase from the ampC gene of Enterobacter cloacae P99 and comparison with a class A penicillinase.

1993 • 194 citations

The Aeromonas hydrophila cphA gene: molecular heterogeneity among class B metallo-beta-lactamases

1991 • 183 citations

PENICILLINASE-PRODUCING GONOCOCCI IN LIVERPOOL

1976 • 182 citations

β‐Lactamase of Bacillus licheniformis 749/C at 2 Å resolution

1990 • 175 citations

Amino Acid Sequence Determinants of β-Lactamase Structure and Activity

1996 • 173 citations

Getting to the route of Helicobacter pylori treatment

1998 • 172 citations

The mechanism of catalysis and the inhibition of the Bacillus cereus zinc-dependent β-lactamase

1998 • 166 citations

The Antimicrobial Agents Annual/2.

1987 • 164 citations

Comparative activities of clavulanic acid, sulbactam, and tazobactam against clinically important beta-lactamases

1994 • 161 citations

Sequence of PSE-2 beta-lactamase

1988 • 156 citations

Biochemical characterization of a beta-lactamase that hydrolyzes penems and carbapenems from two Serratia marcescens isolates

1990 • 155 citations

A regulatory gene (ccaR) required for cephamycin and clavulanic acid production in Streptomyces clavuligerus: amplification results in overproduction of both beta-lactam compounds

1997 • 155 citations

Structural Basis for Clinical Longevity of Carbapenem Antibiotics in the Face of Challenge by the Common Class A β-Lactamases from the Antibiotic-Resistant Bacteria

1998 • 150 citations

Biochemical properties of a carbapenem-hydrolyzing beta-lactamase from Enterobacter cloacae and cloning of the gene into Escherichia coli

1993 • 150 citations

Cardiac arrest and acidosis.

1962 • 147 citations

Chemistry and biosynthesis of clavulanic acid and other clavams

1997 • 146 citations

A natural polymorphism in β-lactamase is a global suppressor

1997 • 144 citations

Inactivation of class A .beta.-lactamases by clavulanic acid: the role of arginine-244 in a proposed nonconcerted sequence of events

1993 • 135 citations

The purification and properties of a penicillinase whose synthesis is mediated by an R-factor in Escherichia coli

1966 • 133 citations

A potent new mode of β-lactamase inhibition revealed by the 1.7 Å X-ray crystallographic structure of the TEM-1–BLIP complex

1996 • 132 citations

Molecular evolution of bacterial β-lactam resistance

1996 • 128 citations

Crystal Structure of 6α-(Hydroxymethyl)penicillanate Complexed to the TEM-1 β-Lactamase from Escherichia coli: Evidence on the Mechanism of Action of a Novel Inhibitor Designed by a Computer-Aided Process

1996 • 123 citations

Emergence of clinical isolates of Escherichia coli producing TEM-1 derivatives or an OXA-1 beta-lactamase conferring resistance to beta-lactamase inhibitors

1994 • 123 citations

Nucleotide sequences of the genes coding for the TEM-like β-lactamases IRT-1 and IRT-2 (formerly called TRI-1 and TRI-2)

1994 • 122 citations

Molecular characterization of nine different types of mutants among 107 inhibitor-resistant TEM beta-lactamases from clinical isolates of Escherichia coli

1995 • 120 citations

Clinical isolates of Escherichia coli producing TRI β-lactamases: novel TEM-enzymes conferring resistance to β-lactamase inhibitors

1992 • 119 citations

Biochemical comparison of imipenem, meropenem and biapenem: permeability, binding to penicillin-binding proteins, and stability to hydrolysis by β-lactamases

1995 • 119 citations

In vitro antibacterial activity of SM-7338, a carbapenem antibiotic with stability to dehydropeptidase I

1989 • 116 citations

A complex mutant of TEM-1 beta-lactamase with mutations encountered in both IRT-4 and extended-spectrum TEM-15, produced by an Escherichia coli clinical isolate

1997 • 114 citations

Resistance caused by decreased penetration of beta-lactam antibiotics into Enterobacter cloacae

1985 • 112 citations

EVIDENCE FOR TWO DISTINCT TYPES OF PENICILLINASE-PRODUCING NEISSERIA GONORRHή

1977 • 110 citations

Inhibition of TEM-2 β-Lactamase from Escherichia coli by Clavulanic Acid: Observation of Intermediates by Electrospray Ionization Mass Spectrometry^,

1996 • 109 citations

Binding of Thienamycin and Clavulanic Acid to the Penicillin-Binding Proteins of Escherichia coli K-12

1977 • 108 citations

Isolation and characterization of a beta-lactamase-inhibitory protein from Streptomyces clavuligerus and cloning and analysis of the corresponding gene

1990 • 108 citations

Plasmid-Mediated -Lactamase (TEM-7) Involved in Resistance to Ceftazidime and Aztreonam

1988 • 107 citations

Role of Ser-238 and Lys-240 in the hydrolysis of third-generation cephalosporins by SHV-type beta-lactamases probed by site-directed mutagenesis and three-dimensional modeling.

1993 • 106 citations

Emergence of an inhibitor-resistant beta-lactamase (SHV-10) derived from an SHV-5 variant

1997 • 105 citations

Substitution of lysine at position 104 or 240 of TEM-1pTZ18R .beta.-lactamase enhances the effect of serine-164 substitution on hydrolysis or affinity for cephalosporins and the monobactam aztreonam

1991 • 97 citations

Imipenem/Cilastatin

1992 • 96 citations

Genetics and Molecular Biology of β-Lactam-Resistant Pneumococci

1995 • 94 citations

Resistance to Cefamandole: Derepression of -Lactamases by Cefoxitin and Mutation in Enterobacter cloacae

1982 • 94 citations

Biochemical characterization of the metallo-beta-lactamase CcrA from Bacteroides fragilis TAL3636

1992 • 88 citations

The role of lysine-234 in .beta.-lactamase catalysis probed by site-directed mutagenesis

1990 • 87 citations

Olivanic acids, a family of .BETA.-lactam antibiotics with .BETA.-lactamase inhibitory properties produced by Streptomyces species. I. Detection, properties and fermentation studies.

1979 • 82 citations

A Structure-Based Analysis of the Inhibition of Class A .beta.-Lactamases by Sulbactam

1994 • 80 citations

Chemical studies on the inactivation of Escherichia coli RTEM β-lactamase by clavulanic acid

1978 • 80 citations

Inhibition of the mammalian .beta.-lactamase renal dipeptidase (dehydropeptidase-I) by Z-2-(acylamino)-3-substituted-propenoic acids

1987 • 79 citations

Conjugal transfer of imipenem resistance in Bacteroides fragilis.

1992 • 76 citations

Inhibition of the RTEM .beta.-lactamase from Escherichia coli. Interaction of the enzyme with derivatives of olivanic acid

1982 • 70 citations

Inhibition of the RTEM .beta.-lactamase from Escherichia coli. Interaction of the enzyme with derivatives of olivanic acid

1981 • 70 citations

First characterization of inhibitor-resistant TEM (IRT) beta-lactamases in Klebsiella pneumoniae strains

1995 • 65 citations

The Role of Tyrosine 150 in Catalysis of .beta.-Lactam Hydrolysis by AmpC .beta.-Lactamase from Escherichia coli Investigated by Site-Directed Mutagenesis

1994 • 64 citations

Nuances of Mechanisms and Their Implications for Evolution of the Versatile β-Lactamase Activity: From Biosynthetic Enzymes to Drug Resistance Factors

1997 • 63 citations

Augmentin (amoxycillin and clavulanic acid) therapy in complicated infections due to β-lactamase producing bacteria

1981 • 61 citations

Penicillin-binding proteins. Wall peptidoglycan assembly and resistance to penicillin: facts, doubts and hopes

1997 • 61 citations

The roles of residues Tyr150, Glu272, and His314 in class C β‐lactamases

1996 • 61 citations

Molecular epidemiology of TEM-3 (CTX-1) beta-lactamase

1990 • 58 citations

Mechanism of turnover of imipenem by the TEM .beta.-lactamase revisited

1995 • 56 citations

The inhibition of β-lactamases from Gram-negative bacteria by clavulanic acid

1981 • 52 citations

Biochemical characteristics of extended broad spectrum β-lactamases

1989 • 51 citations

Design, Synthesis, and Evaluation of a Potent Mechanism-Based Inhibitor for the TEM .beta.-Lactamase with Implications for the Enzyme Mechanism

1995 • 48 citations

Imipenem and cephem resistant Pseudomonas aeruginosa carrying plasmids coding for class B β-lactamase

1996 • 48 citations

Facilitation of the .DELTA.2 .fwdarw. .DELTA.1 pyrroline tautomerization of carbapenem antibiotics by the highly conserved arginine-244 of class A .beta.-lactamases during the course of turnover

1992 • 45 citations

Comparative activities of the β-lactamase inhibitors YTR 830, clavulanate and sulbactam combined with extended-spectrum penicillins against ticarcillin-resistant Enterobacteriaceae and pseudomonads

1986 • 45 citations

Penicillin and Beyond: Evolution, Protein Fold, Multimodular Polypeptides, and Multiprotein Complexes

1996 • 43 citations

Distribution of .BETA.-lactam and .BETA.-lactone producing bacteria in nature.

1982 • 41 citations

The disposition and metabolic fate of¹⁴C-meropenem in man

1993 • 38 citations

Clinical trial of the efficacy and safety of ticarcillin and clavulanic acid

1985 • 37 citations

THE DUTCH SOFT-DRUG POLICY

1989 • 37 citations

Comparison of the Substrate Specificities of the β-Lactamases from Klebsiella aerogenes 1082E and Enterobacter cloacae P99

1972 • 37 citations

Characterization of a new TEM-derived beta-lactamase produced in a Serratia marcescens strain

1997 • 36 citations

β-Lactamase mutations far from the active site influence inhibitor binding

1995 • 33 citations

Evidence for Structural Elasticity of Class A β-Lactamases in the Course of Catalytic Turnover of the Novel Cephalosporin Cefepime

1996 • 32 citations

Ciprofloxacin Resistance among Nosocomial Pseudomonas aeruginosa and Staphylococcus aureus in the United States

1995 • 29 citations

β-lactamase activity of renal dipeptidase against N-formimidoyl-thienamycin

1982 • 28 citations

Structure-function relationships among wild-type variants of Staphylococcus aureus beta-lactamase: importance of amino acids 128 and 216

1996 • 28 citations

Effect of Clavulanic Acid on the Minimum Inhibitory Concentration of Benzylpenicillin, Ampicillin, Carbenicillin, or Cephalothin Against Clinical Isolates Resistant to Beta-Lactam Antibiotics

1979 • 27 citations

Complementary roles of mutations at positions 69 and 242 in a class A β-lactamase

1995 • 25 citations

Factors affecting methicillin resistance in Staphylococcus aureus

1995 • 24 citations

Izumenolide - a novel .BETA.-lactamase inhibitor produced by Micromonospora. II. Biological properties.

1980 • 23 citations

Interactions between active‐site serine β‐lactamases and so‐called β‐lactamase‐stable antibiotics

1993 • 20 citations

Improved sensitivity in assays for binding of novel beta-lactam antibiotics to penicillin-binding proteins of Escherichia coli

1987 • 19 citations

Quantification of the extent of attenuation of the rate of turnover chemistry of the TEM-1 β-lactamase by the α-1R-hydroxyethyl group in substrates

1996 • 17 citations

Importance of Antimicrobial Susceptibility Testing of Streptococcus pneumoniae

1978 • 16 citations

Comparative amino acid contents of purified β‐lactamases from enteric bacteria

1970 • 15 citations

β-Lactamase stability of cefoxitin in comparison with other β-lactam compounds

1983 • 13 citations

Mass Spectrometric Studies on the Inhibition of TEM-2.BETA.-Lactamase by Clavulanic Acid Derivatives.

1997 • 11 citations

Comparison of the Substrate Specificities of the β-Lactamases from Klebsiella aerogenes 1082E and Enterobacter cloacae P99

1972 • 11 citations

The Efficacy and Safety of Imipenem/Cilastatin in the Treatment of Severe Bacterial Infections

1990 • 4 citations