Catalytic promiscuity and the evolution of new enzymatic activities

SCOP: A structural classification of proteins database for the investigation of sequences and structures

1995 • 6,372 citations

Evolution by gene duplication

1970 • 5,849 citations

The α/β hydrolase fold

1992 • 2,024 citations

ENZYME RECRUITMENT IN EVOLUTION OF NEW FUNCTION

1976 • 1,071 citations

The evolution of functionally novel proteins after gene duplication

1994 • 974 citations

Reaction mechanism of alkaline phosphatase based on crystal structures

1991 • 930 citations

A Proficient Enzyme

1995 • 859 citations

DNA shuffling of a family of genes from diverse species accelerates directed evolution

1998 • 821 citations

Enzymatic Reaction Mechanisms

1978 • 810 citations

Comprehensive biological catalysis

1998 • 647 citations

2 Evolutionary and Structural Relationships among Dehydrogenases

1975 • 607 citations

Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities.

1991 • 584 citations

Comparative anatomy of the aldo–keto reductase superfamily

1997 • 582 citations

Structural Insights into the Evolution of an Antibody Combining Site

1997 • 550 citations

An evolutionary treasure: unification of a broad set of amidohydrolases related to urease

1997 • 491 citations

CPx-type ATPases: a class of P-type ATPases that pump heavy metals

1996 • 472 citations

A single amino acid substitution converts a carboxylesterase to an organophosphorus hydrolase and confers insecticide resistance on a blowfly

1997 • 381 citations

The evolution of α/β barrel enzymes

1990 • 378 citations

Reactivity of Nucleophilic Reagents toward Esters

1960 • 374 citations

X-ray structure of a vanadium-containing enzyme: chloroperoxidase from the fungus Curvularia inaequalis.

1996 • 370 citations

Evolutionary relationships among pyridoxal‐5′‐phosphate‐dependent enzymes

1994 • 368 citations

PSEUDOALLELISM AND GENE EVOLUTION

1951 • 358 citations

Pyridoxal phosphate-dependent enzymes

1995 • 344 citations

The Recruitment of Crystallins: New Functions Precede Gene Duplication

1991 • 335 citations

A Deoxyribonucleic Acid Phosphatase-Exonuclease from Escherichia coli

1964 • 332 citations

Crystal Structure of Human Arylsulfatase A: The Aldehyde Function and the Metal Ion at the Active Site Suggest a Novel Mechanism for Sulfate Ester Hydrolysis^,

1998 • 320 citations

Computer Analysis of Bacterial Haloacid Dehalogenases Defines a Large Superfamily of Hydrolases with Diverse Specificity

1994 • 310 citations

Structure of a human lysosomal sulfatase

1997 • 299 citations

The Enolase Superfamily: A General Strategy for Enzyme-Catalyzed Abstraction of the α-Protons of Carboxylic Acids

1996 • 297 citations

Understanding Enzyme Superfamilies

1997 • 280 citations

Directed evolution of a fucosidase from a galactosidase by DNA shuffling and screening

1997 • 275 citations

Implications for the Catalytic Mechanism of the Vanadium-Containing Enzyme Chloroperoxidase from the Fungus Curvularia inaequalis by X-Ray Structures of the Native and Peroxide Form

1997 • 275 citations

Catalytic Plasticity of Fatty Acid Modification Enzymes Underlying Chemical Diversity of Plant Lipids

1998 • 259 citations

The catalytic domain of the P-type ATPase has the haloacid dehalogenase fold

1998 • 258 citations

Cobalt(III) complex-promoted hydrolysis of phosphate diesters: comparison in reactivity of rigid cis-diaquo(tetraaza)cobalt(III) complexes

1989 • 247 citations

Analogous Enzymes: Independent Inventions in Enzyme Evolution

1998 • 241 citations

Identification of a novel phosphatase sequence motif

1997 • 239 citations

How far divergent evolution goes in proteins

1998 • 236 citations

Transition metal ion inhibition of enzyme-catalyzed phosphate ester displacement reactions

1974 • 200 citations

Directed evolution of an aspartate aminotransferase with new substrate specificities

1998 • 196 citations

The protein phosphatase 2C (PP2C) superfamily: Detection of bacterial homologues

1996 • 195 citations

The Reactivity of Nucleophilic Reagents toward the p-Nitrophenyl Phosphate Dianion¹

1965 • 190 citations

Off-the-shelf proteins that rival tailor-made antibodies as catalysts

1996 • 172 citations

From phosphatases to vanadium peroxidases: A similar architecture of the active site

1997 • 165 citations

Acetylation of human serum albumin by p-nitrophenyl acetate

1975 • 164 citations

A Single Amino Acid Substitution, Gly117His, Confers Phosphotriesterase (Organophosphorus Acid Anhydride Hydrolase) Activity on Human Butyrylcholinesterase

1997 • 161 citations

Autotaxin Is an Exoenzyme Possessing 5′-Nucleotide Phosphodiesterase/ATP Pyrophosphatase and ATPase Activities

1997 • 159 citations

Structural conservation in parallel .beta./.alpha.-barrel enzymes that catalyze three sequential reactions in the pathway of tryptophan biosynthesis

1991 • 158 citations

The structure and evolution of a/β barrel proteins

1995 • 157 citations

A superfamily of metalloenzymes unifies phosphopentomutase and cofactor‐independent phosphoglycerate mutase with alkaline phosphatases and sulfatases

1998 • 156 citations

A novel family of predicted phosphoesterases includes Drosophila prune protein and bacterial recJ exonuclease

1998 • 153 citations

Evolutionary recruitment of biochemically specialized subdivisions of Family I within the protein superfamily of aminotransferases

1996 • 153 citations

The phosphatase activity of carbonic anhydrase III is reversibly regulated by glutathiolation.

1996 • 148 citations

Carbonic Anhydrase III. OXIDATIVE MODIFICATION IN VIVO AND LOSS OF PHOSPHATASE ACTIVITY DURING AGING

1995 • 145 citations

Fosfomycin Resistance Protein (FosA) Is a Manganese Metalloglutathione Transferase Related to Glyoxalase I and the Extradiol Dioxygenases

1997 • 141 citations

A Functionally Diverse Enzyme Superfamily that Abstracts the α Protons of Carboxylic Acids

1995 • 138 citations

A duplicated catalytic motif in a new superfamily of phosphohydrolases and phospholipid synthases that includes poxvirus envelope proteins

1996 • 135 citations

An unexpected structural relationship between integral membrane phosphatases and soluble haloperoxidases

1997 • 134 citations

Mandelate racemase and muconate lactonizing enzyme are mechanistically distinct and structurally homologous

1990 • 128 citations

On the origin of enzymatic species

1993 • 124 citations

Vanadium haloperoxidases

1998 • 119 citations

A new family of carbon‐nitrogen hydrolases

1994 • 115 citations

Sulfatase Activity of E. coli Alkaline Phosphatase Demonstrates a Functional Link to Arylsulfatases, an Evolutionarily Related Enzyme Family

1998 • 114 citations

Design and expression of organophosphorus acid anhydride hydrolase activity in human butyrylcholinesterase

1995 • 111 citations

Catalytic Mechanism of the Metal-dependent Fuculose Aldolase fromEscherichia colias Derived from the Structure

1996 • 110 citations

Organophosphorus Acid Anhydride Hydrolase Activity in Human Butyrylcholinesterase: Synergy Results in a Somanase

1998 • 110 citations

Crystal structures ofBacillus stearothermophilus adenylate kinase with bound Ap5A, Mg2+ Ap5A, and Mn2+ Ap5A reveal an intermediate lid position and six coordinate octahedral geometry for bound Mg2+ and Mn2+

1998 • 109 citations

A highly active decarboxylating dehydrogenase with rationally inverted coenzyme specificity.

1995 • 108 citations

Mechanism of cyanogenesis: the crystal structure of hydroxynitrile lyase from Hevea brasiliensis

1996 • 106 citations

In vitro evolution of horse heart myoglobin to increase peroxidase activity

1998 • 105 citations

Evolution of biosynthetic pathways: a common ancestor for threonine synthase, threonine dehydratase and D-serine dehydratase.

1986 • 104 citations

Conversion of Myoglobin into a Peroxygenase: A Catalytic Intermediate of Sulfoxidation and Epoxidation by the F43H/H64L Mutant

1997 • 100 citations

Escherichia coli L-asparaginase. Catalytic activity and subunit nature

1970 • 99 citations

Crystal structure of enolase indicates that enolase and pyruvate kinase evolved from a common ancestor

1988 • 97 citations

Conversion of Myoglobin into a Highly Stereo- specific Peroxygenase by the L29H/H64L Mutation

1996 • 96 citations

Protein engineering reveals ancient adaptive replacements in isocitrate dehydrogenase

1997 • 96 citations

Mechanistically diverse enzyme superfamilies: the importance of chemistry in the evolution of catalysis

1998 • 94 citations

Inhibition of phosphatase and sulfatase by transition-state analogs

1988 • 92 citations

Enantioselective sulfoxidation mediated by vanadium-incorporated phytase: a hydrolase acting as a peroxidase

1998 • 91 citations

The cytidylyltransferase superfamily: Identification of the nucleotide-binding site and fold prediction

1995 • 84 citations

Evolution of Enzymatic Activities in the Enolase Superfamily: Characterization of the (D)-Glucarate/Galactarate Catabolic Pathway in Escherichia coli

1998 • 81 citations

Evolution of an enzyme active site: The structure of a new crystal form of muconate lactonizing enzyme compared with mandelate racemase and enolase

1998 • 81 citations

A Cytosine Methyltransferase Converts 5-Methylcytosine in DNA to Thymine

1995 • 81 citations

2 Chemical Modification by Active-Site-Directed Reagents

1970 • 80 citations

Phosphodiesterase activity is a novel property of alkaline phosphatase from osseous plate

1994 • 77 citations

Identification of Functional Residues in a 2-Hydroxymuconic Semialdehyde Hydrolase

1995 • 75 citations

Biochemistry of esterases associated with organophosphate resistance in Lucilia cuprina with comparisons to putative orthologues in other Diptera.

1997 • 74 citations

Insights into the Mechanism of Catalysis by the P−C Bond-Cleaving Enzyme Phosphonoacetaldehyde Hydrolase Derived from Gene Sequence Analysis and Mutagenesis

1998 • 74 citations

The p-nitrophenyl phosphatase activity of muscle carbonic anhydrase

1981 • 72 citations

An α/β-barrel full of evolutionary trouble

1993 • 71 citations

Reaction of L-serine O-sulfate with aspartate aminotransferase

1969 • 71 citations

Engineering cyclophilin into a proline-specific endopeptidase

1998 • 69 citations

Common ancestry of Escherichia coli pyruvate oxidase and the acetohydroxy acid synthases of the branched-chain amino acid biosynthetic pathway

1988 • 67 citations

Preparation and Reactions of Myoglobin Mutants Bearing both Proximal Cysteine Ligand and Hydrophobic Distal Cavity: Protein Models for the Active Site of P-450

1996 • 66 citations

Engineering Steroid 5β-Reductase Activity into Rat Liver 3α-Hydroxysteroid Dehydrogenase

1998 • 64 citations

Evolutionary link between glycogen phosphorylase and a DNA modifying enzyme.

1995 • 63 citations

Albumin-Catalyzed Proton Transfer

1996 • 63 citations

Alternating arginine-modulated substrate specificity in an engineered tyrosine aminotransferase

1995 • 61 citations

Jack bean urease (EC 3.5.1.5) VIII. On the inhibition of urease by amides and esters of phosphoric acid

1986 • 60 citations

Mechanisms of interaction of Escherichia coli threonine synthase with substrates and inhibitors

1994 • 60 citations

Threonine Synthetase of Bacillus subtilis

1973 • 58 citations

Engineering nitrile hydratase activity into a cysteine protease by a single mutation

1995 • 56 citations

The reactivity of his-57 in chymotrypsin to alkylation

1971 • 52 citations

Can homologous proteins evolve different enzymatic activities?

1993 • 51 citations

Hydrolysis of Phosphodiesters through Transformation of the Bacterial Phosphotriesterase

1998 • 50 citations

Active-site Arg → Lys Substitutions Alter Reaction and Substrate Specificity of Aspartate Aminotransferase

1997 • 49 citations

Reversal of substrate charge specificity by site-directed mutagenesis of aspartate aminotransferase

1987 • 49 citations

Effective charge distribution for attack of phenoxide ion on aryl methyl phosphate monoanion: studies related to the action of ribonuclease

1989 • 46 citations

New enzyme lineages by subdomain shuffling

1998 • 44 citations

Mechanistic imperatives for the evolution of glutathione transferases

1998 • 44 citations

Determinants of Substrate Specificity in the Superfamily of Amino Acid Dehydrogenases^,

1997 • 43 citations

Epimerization via Carbon−Carbon Bond Cleavage. <scp>l</scp>-Ribulose-5-phosphate 4-Epimerase as a Masked Class II Aldolase

1998 • 41 citations

Catalytic hydrolysis of cAMP

1987 • 40 citations

The pepsin-catalyzed hydrolysis of sulfite esters

1967 • 39 citations

Identity of Phosphodiesterase and Phosphomonoesterase Activities with Nuclease P1 (a Nuclease from Penicillium citrinum)

1974 • 39 citations

Changing the Reaction Specificity of a Pyridoxal-5'-phosphate-dependent Enzyme

1995 • 36 citations

Specific arginine modification at the phosphatase site of muscle carbonic anhydrase

1985 • 34 citations

Alkaline phosphatase possessing alkaline phosphodiesterase activity and other phosphodiesterases in Bacillus subtilis

1978 • 33 citations

Identity of Phosphodiesterase and Phosphomonoesterase Activities with Nuclease P1 (a Nuclease from Penicillium citrinum)

1974 • 32 citations

The major acidic fibroblast growth factor (aFGF)-stimulated phosphoprotein from bovine liver plasma membranes has aFGF-stimulated kinase, autoadenylylation, and alkaline nucleotide phosphodiesterase activities.

1993 • 31 citations

Modification of .alpha.-chymotrypsin by methyl p-nitrobenzenesulfonate

1969 • 31 citations

Changing the Reaction Specificity of a Pyridoxal-5'-phosphate-dependent Enzyme

1995 • 30 citations

Redesign of Choline Acetyltransferase Specificity by Protein Engineering

1998 • 30 citations

Catalytic recruitment in the inactivation of serine proteases by phosphonate esters. Recruitment of acid-base catalysis

1986 • 29 citations

Sulfuryl transfer catalyzed by pyruvate kinase

1989 • 27 citations

Partial reversal of the substrate stereospecificity of an L-lactate dehydrogenase by site-directed mutagenesis

1995 • 26 citations

Polynucleotide Ligase Activity of Eukaryotic Topoisomerase I

1998 • 25 citations

Evolution of Enzymatic Activities in the Enolase Superfamily: Crystal Structure of (D)-Glucarate Dehydratase from Pseudomonas putida^,

1998 • 25 citations

Enantioselective and Reversible Inhibition of Trypsin and .alpha.-Chymotrypsin by Phosphonate Esters

1994 • 25 citations

Refined High-Resolution Structure of the Metal-Ion Dependent L-Fuculose-1-phosphate Aldolase (Class II) from Escherichia coli

1996 • 25 citations

Oxonase and esterase activities of erythrocyte carbonic anhydrase

1978 • 25 citations

The reactivity of p-nitrophenyl acetate with serum albumins

1988 • 24 citations

A common origin for enzymes involved in the terminal step of the threonine and tryptophan biosynthetic pathways.

1987 • 24 citations

Catalytic Activity of the N-Terminal Domain ofEscherichia coliAsparagine Synthetase B Can Be Reengineered by Single-Point Mutation

1997 • 22 citations

Evolution of Enzymatic Activities: Multiple Pathways for Generating and Partitioning a Common Enolic Intermediate by Glucarate Dehydratase from Pseudomonas putida

1996 • 21 citations

Cloning, DNA sequencing and heterologous expression of the gene for thermostable N-acylamino acid racemase from Amycolatopsis sp. TS-1-60 in Escherichia coli

1995 • 21 citations

Cloning, DNA sequencing and heterologous expression of the gene for thermostable N -acylamino acid racemase from Amycolatopsis sp. TS-1-60 in Escherichia coli

1995 • 20 citations

Engineering for redesign

1994 • 18 citations

Enzymology and genetic regulation of a cyclic nucleotide-binding phosphodiesterase-phosphomonoesterase from Aspergillus nidulans

1975 • 16 citations

Repressible alkaline phosphatase from Thermus aquaticus: associated phosphodiesterase activity.

1977 • 16 citations

Evolution of Enzymatic Activities in the Enolase Superfamily: Partitioning of Reactive Intermediates by (D)-Glucarate Dehydratase from Pseudomonas putida

1998 • 16 citations

3′,5′-Cyclic nucleotide phosphodiesterase activity of the sulphatase A of ox liver

1981 • 13 citations

The reactivity of metal-hydroxo nucleophiles and a range of bases in the hydrolysis of the phosphate triester 2,4-dinitrophenyl diethyl phosphate

1996 • 12 citations

Evidence for Induced Fit of a Pseudo‐Substrate of Aspartate Aminotransferase

1972 • 11 citations

Sulfuryl transfer catalyzed by phosphokinases

1991 • 11 citations