Current Protein & Peptide Science[JOURNAL]
Sun
168 papers
The synthesis and study of side-chain lactam-bridged peptides.
Taylor JW
Biopolymers · 2002 · PMID 12228920 · Publisher ↗
Side-chain lactam bridges linking amino acid residues that are spaced several residues apart in the linear sequence offer a convenient and flexible method for introducing conformational constraints into a peptide structu...
Side-chain lactam bridges linking amino acid residues that are spaced several residues apart in the linear sequence offer a convenient and flexible method for introducing conformational constraints into a peptide structure. The availability of a variety of selectively cleavable protecting groups for amines and carboxylic acids allows for several approaches to the synthesis of monocyclic, dicyclic, and bicyclic lactam-bridged peptides by solid-phase methods. Multicyclic structures are also accessible, but segment-condensation syntheses with solution-phase cyclizations are most likely to provide the best synthetic approach to these more complex constrained peptides. Lactam bridges linking (i, i + 3)-, (i, i + 4), and (i, i + 7)-spaced residue pairs have all proven useful for stabilization of alpha helices, and (i, i + 3)-linked residues have also been demonstrated to stabilize beta-turns. These structures are finding an increasing number of applications in protein biology, including studies of protein folding, protein aggregation, peptide ligand-receptor recognition, and the development of more potent peptide therapeutics. Defining the functional roles of the amphiphilic alpha-helices in medium-sized peptide hormones, and studying helix propagation from rigid, alpha-helix initiating bicyclic peptides are among the most exciting developments currently underway in this field.
Control of peptide conformation by the Thorpe-Ingold effect (C alpha-tetrasubstitution).
Toniolo C, Crisma M, Formaggio F … +1 more , Peggion C
Biopolymers · 2001 · PMID 12209474 · Publisher ↗
The preferred conformations of peptides heavily based on the currently extensively exploited achiral and chiral alpha-amino acids with a quaternary alpha-carbon atom, as determined by conformational energy computations,...
The preferred conformations of peptides heavily based on the currently extensively exploited achiral and chiral alpha-amino acids with a quaternary alpha-carbon atom, as determined by conformational energy computations, crystal-state (x-ray diffraction) analyses, and solution ((1)H-NMR and spectroscopic) investigations, are reviewed. It is concluded that 3(10)/alpha-helical structures and the fully extended (C(5)) conformation are preferentially adopted by peptide sequences characterized by this family of amino acids, depending upon overall bulkiness and nature (e.g., whether acyclic or C(alpha) (i) <--> C(alpha) (i) cyclized) of their side chains. The intriguing relationship between alpha-carbon chirality and bend/helix handedness is also illustrated. gamma-Bends and semiextended conformations are rarely observed. Formation of beta-sheet structures is prevented.
Alzheimer beta-amyloid peptides: structures of amyloid fibrils and alternate aggregation products.
Gorman PM, Chakrabartty A
Biopolymers · 2001 · PMID 12115148 · Publisher ↗
The amyloidoses are a heterogeneous group of diseases, which are characterized by the local or systemic deposition of amyloid. At the root of these diseases are changes in protein conformation where normal innocuous prot...
The amyloidoses are a heterogeneous group of diseases, which are characterized by the local or systemic deposition of amyloid. At the root of these diseases are changes in protein conformation where normal innocuous proteins transform into insoluble amyloid fibrils and deposit in tissues. The amyloid fibrils of Alzheimer's disease are composed of the Abeta peptide and deposit in the form of senile plaques. Neurodegeneration surrounds the amyloid deposits, indicating that neurotoxic substances are produced during the deposition process. Whether the neurotoxic species is the amyloid fibril or a fibril precursor is a current area of active research. This review focuses on advancements made in elucidating the molecular structures of the Abeta amyloid fibril and alternate aggregation products of the Abeta peptide formed during fibrillogenesis.
The binding database: overview and user's guide.
Chen X, Lin Y, Gilson MK
Biopolymers · 2001-2002 · PMID 11987162 · Publisher ↗
The large and growing body of experimental data on molecular binding is of enormous value in biology, pharmacology, and chemistry. Applications include the assignment of function to biomolecules, drug discovery, molecula...
The large and growing body of experimental data on molecular binding is of enormous value in biology, pharmacology, and chemistry. Applications include the assignment of function to biomolecules, drug discovery, molecular modeling, and nanotechnology. However, binding data are difficult to find and access because they are available almost exclusively through scientific journals. BindingDB, a public, web-accessible database of measured binding affinities, is designed to address this problem. BindingDB collects data for natural and modified biomolecules and for synthetic compounds, and provides detailed experimental information. Currently, measurements by isothermal titration calorimetry are fully supported; measurements by enzyme inhibition will soon be included as well. The web site allows data to be searched by a range of criteria, including binding thermodynamics, sequence homology, and chemical structure, substructure, and similarity. Experimentalists are encouraged to publicize their data by entering it into BindingDB via the online forms. Such data can be updated or revised by the depositor, if necessary, and will remain publicly accessible. User involvement and feedback are welcomed.
Cation-pi interaction in a folded polypeptide.
Burghardt TP, Juranić N, Macura S … +1 more , Ajtai K
Biopolymers · 2002 Apr · PMID 11807753 · Publisher ↗
Cationic and aromatic side chains from protein residues interact to stabilize tertiary structure. The stabilization energy originates in part from electrostatic attraction between the cation, and regions of high electron...
Cationic and aromatic side chains from protein residues interact to stabilize tertiary structure. The stabilization energy originates in part from electrostatic attraction between the cation, and regions of high electron density in pi-orbitals of the aromatic group, leading to the name cation-pi interaction. The lysine and tyrosine containing peptide, N-acetyl-Pro-Pro-Lys-Tyr-Asp-Lys-NH(2), has near uv CD characteristic of tyrosine in a structured environment. Nuclear Overhauser effect (NOE), coupling constant, and ring current chemical shift constraints obtained with (1)H NMR confirm that the peptide (t6p) folds. Simulated annealing consistent with all NMR constraints produces a 40-structure ensemble for t6p with potential energies within one standard deviation of the lowest value observed. Calculated binding energies indicate that cation-pi and cation-phenolic OH interactions exists between the Lys3 and Tyr4 side chains in most of the structures. The t6p peptide in solution is a model for these interactions in a protein. A perturbing electric field from the cationic ground state charge intermingles the excited states of the aromatic group. This intermingling effect may provide a cation-pi signature effect in the tyrosine spectroscopy. The absorption and CD for the lowest energy electronic transitions of the tyrosine phenol were computed for the ensemble. Red-shifted peak energy and hypochromicity in the absorbance band, and decreasing rotational strength, correlates with increasing binding energy of the complex indicating the cation-pi spectroscopic signature. The ensemble average spectroscopic signature effects in t6p are small and in agreement with observation.
Development and current status of the CHARMM force field for nucleic acids.
MacKerell AD, Banavali N, Foloppe N
Biopolymers · 2000-2001 · PMID 11754339 · Publisher ↗
The CHARMM27 all-atom force field for nucleic acids represents a highly optimized model for investigations of nucleic acids via empirical force field calculations. The force field satisfactorily treats the A, B, and Z fo...
The CHARMM27 all-atom force field for nucleic acids represents a highly optimized model for investigations of nucleic acids via empirical force field calculations. The force field satisfactorily treats the A, B, and Z forms of DNA as well as RNA, and it also useful for nucleosides and nucleotides. In addition, it is compatible with the CHARMM force fields for proteins and lipids, allowing for simulation studies of heterogeneous systems.
Editorial: current developments in computational studies of peptides.
Nikiforovich GV, Marshall GR
Biopolymers · 2001 · PMID 11455543 · Publisher ↗
Abstract loading — click title to view on PubMed.
Prediction of the subcellular location of prokaryotic proteins based on a new representation of the amino acid composition.
Feng ZP
Biopolymers · 2001 Apr · PMID 11241220 · Publisher ↗
A new representation of protein sequence is devoted in this paper, in which each protein can be represented by a 20-dimensional (20D) vector of unit length. Inspired by the principle of superposition of state in quantum...
A new representation of protein sequence is devoted in this paper, in which each protein can be represented by a 20-dimensional (20D) vector of unit length. Inspired by the principle of superposition of state in quantum mechanics, the squares of the 20 components of the vector correspond to the amino acid composition. Using the new representation of the primary sequence and Bayes Discriminant Algorithm, the subcellular location of prokaryotic proteins was predicted. The overall predictive accuracy in the jackknife test can be 3% higher than the result of using amino acid composition directly for the database of sequence identity is less than 90%, but 5% higher when sequence identity is less than 80%. The higher predictive accuracy indicates that the current measure of extracting the information from the primary sequence is efficient. Since the subcellular location restricting a protein's possible function, the present method should also be a useful measure for the systematic analysis of genome data. The program used in this paper is available on request.
Cation recognition by self-assembled monolayers of oriented helical peptides having a crown ether unit.
Miura Y, Kimura S, Kobayashi S … +2 more , Imanishi Y, Umemura J
Biopolymers · 2000 · PMID 11241214 · Publisher ↗
Cation recognition of self-assembled monolayers (SAMs) of helical peptides having a crown ether unit was investigated by the impedance spectroscopy and cyclic voltammetry. Lipo-(Ala-Aib)8-Ala-Cr and Boc-Glu(Cr)-(Ala-Aib)...
Cation recognition of self-assembled monolayers (SAMs) of helical peptides having a crown ether unit was investigated by the impedance spectroscopy and cyclic voltammetry. Lipo-(Ala-Aib)8-Ala-Cr and Boc-Glu(Cr)-(Ala-Aib)8-Lipoa (Lipo, Lipoa, and Cr represent lipoic acid, lipoamide, and amidobenzo-18-crown-6, respectively) were synthesized and the helix SAMs were prepared. The peptides having a crown ether unit formed SAMs oriented nearly vertically to the substrate. The capacitance of the Lipo-(Ala-Aib)(8)-Ala-Cr SAM changed specifically with the addition of cations, and the binding constants of the SAM were larger than those of the crown ether in aqueous solution because of a large dipole moment of the helical peptide. In the case of the Boc-Glu(Cr)-(Ala-Aib)8-Lipoa SAM, the cation binding to the SAM showed a drastic decrease in the peak current of the cyclic voltammetry around 10(-5)M of K+ ion. In either capacitance measurement or cyclic voltammetry, the helical peptide SAM played an important role in the sensitive response to cations.
The human interferon alpha species and receptors.
Pestka S
Biopolymers · 2000 · PMID 11169919 · Publisher ↗
Interferon (IFN) was approved by the U.S. Food and Drug Administration on June 5, 1986. As the first biotherapeutic approved, IFN-alpha paved the way for development of many other cytokines and growth factors. Neverthele...
Interferon (IFN) was approved by the U.S. Food and Drug Administration on June 5, 1986. As the first biotherapeutic approved, IFN-alpha paved the way for development of many other cytokines and growth factors. Nevertheless, we have just touched the surface of understanding the multitude of human IFNs. This paper reviews the history of the purification of human leukocyte IFN and key aspects of our current state of knowledge of human interferon alpha genes, proteins, and receptors.
FTIR microscopic imaging of collagen and proteoglycan in bovine cartilage.
Camacho NP, West P, Torzilli PA … +1 more , Mendelsohn R
Biopolymers · 2001 · PMID 11135186 · Publisher ↗
Articular cartilage, a connective tissue that provides resistance to compressive forces during joint movements, has not been examined in detail by conventional Fourier transform infrared (FTIR) spectroscopy, microspectro...
Articular cartilage, a connective tissue that provides resistance to compressive forces during joint movements, has not been examined in detail by conventional Fourier transform infrared (FTIR) spectroscopy, microspectroscopy (FTIRM), or imaging (FTIRI). The current study reports FTIRM and FTIRI analyses of normal bovine cartilage and identifies the specific molecular components of cartilage that contribute to its IR spectrum. FTIRM data acquired through the superficial, middle, and deep zones of thin sections of bovine articular cartilage showed a variation in intensities of the absorbance bands that arise from the primary nonaqueous components of cartilage, collagen, and proteoglycan (primarily aggrecan) and thus reflected the differences in quantity of these specific components. The spectra of mixtures of model compounds, which had varying proportions of type II collagen and aggrecan, were analyzed to identify spectral markers that could be used to quantitatively analyze these components in cartilage. Collagen and aggrecan were then imaged by FTIRI based on markers found in the model compounds. Polarization experiments were also performed to determine the spatial distribution of the collagen orientation in the different zones of cartilage. This study provides a framework in which complex pathological changes in this heterogeneous tissue can be assessed by IR microscopic imaging.
Alterations in the chain dynamics of insoluble elastin upon proteolysis by serine elastases.
Samouillan V, Lamure A, Maurel E … +2 more , Lacabanne C, Hornebeck W
Biopolymers · 2001 Feb · PMID 11093116 · Publisher ↗
The high temperature dielectric relaxations of purified and elastolized ligamentum nuchae elastin in the dry state have been investigated by thermally stimulated depolarization current spectrometry, with an equivalent fr...
The high temperature dielectric relaxations of purified and elastolized ligamentum nuchae elastin in the dry state have been investigated by thermally stimulated depolarization current spectrometry, with an equivalent frequency comprised between 10(-2) and 10(-3) Hz. A main relaxation mode, located close to 150 degrees C and attributed to the dielectric manifestation of a glass transition, is found for all samples. After decomposition by the fractional polarization method, the analysis of the high temperature mode shows the existence of two relaxation mechanisms: a cooperative one, associated with flexible zones of the protein, and an isoenthalpic one, corresponding to more ordered and constrained zones. The activation parameters of the two mechanisms are dependent on the extent of elastolysis and on the nature of enzyme (pancreatic elastase vs leukocyte elastase). Both enzymes influence the dielectric behavior of elastin in a similar way: the activation enthalpy maximum of the relaxing units located in the flexible zones, characteristic of the cooperative length, decreases with increasing hydrolysis. Moreover, the isoenthalpic mechanism becomes cooperative at the highest extent of elastolysis, which highlights release of constraints in ordered zones. Nevertheless, the differences found between the two enzymatic hydrolyses are characteristic of distinct sites of cleavage in the elastin network.
Amphipathic, alpha-helical antimicrobial peptides.
Tossi A, Sandri L, Giangaspero A
Biopolymers · 2000 · PMID 10931439 · Publisher ↗
Gene-encoded antimicrobial peptides are an important component of host defense in animals ranging from insects to mammals. They do not target specific molecular receptors on the microbial surface, but rather assume amphi...
Gene-encoded antimicrobial peptides are an important component of host defense in animals ranging from insects to mammals. They do not target specific molecular receptors on the microbial surface, but rather assume amphipathic structures that allow them to interact directly with microbial membranes, which they can rapidly permeabilize. They are thus perceived to be one promising solution to the growing problem of microbial resistance to conventional antibiotics. A particularly abundant and widespread class of antimicrobial peptides are those with amphipathic, alpha-helical domains. Due to their relatively small size and synthetic accessibility, these peptides have been extensively studied and have generated a substantial amount of structure-activity relationship (SAR) data. In this review, alpha-helical antimicrobial peptides are considered from the point of view of six interrelated structural and physicochemical parameters that modulate their activity and specificity: sequence, size, structuring, charge, amphipathicity, and hydrophobicity. It begins by providing an overview of how these vary in peptides from different natural sources. It then analyzes how they relate to the currently accepted model for the mode of action of alpha-helical peptides, and discusses what the numerous SAR studies that have been carried out on these compounds and their analogues can tell us. A comparative analysis of the many alpha-helical, antimicrobial peptide sequences that are now available then provides further information on how these parameters are distributed and interrelated. Finally, the systematic variation of parameters in short model peptides is used to throw light on their role in antimicrobial potency and specificity. The review concludes with some considerations on the potentials and limitations for the development of alpha-helical, antimicrobial peptides as antiinfective agents.
Mutational analysis of the structure and function of opioid receptors.
Law PY, Wong YH, Loh HH
Biopolymers · 1999 · PMID 10797232 · Publisher ↗
The cloning of the opioid receptors allows the investigation of receptor domains involved in the peptidic and nonpeptidic ligand interaction and activation of the opioid receptors. Receptor chimera studies and mutational...
The cloning of the opioid receptors allows the investigation of receptor domains involved in the peptidic and nonpeptidic ligand interaction and activation of the opioid receptors. Receptor chimera studies and mutational analysis of the primary sequences of the opioid receptors have provided insights into the structural domains required for the ligand recognition and receptor activation. In the current review, we examine the current reports on the possible involvement of extracellular domains and transmembrane domains in the high-affinity binding of peptidic and nonpeptidic ligands to the opioid receptor. The structural requirement for the receptors' selectivity toward different ligands is discussed. The receptor domains involved in the activation and subsequent cellular regulation of the receptors' activities as determined by mutational analysis will also be discussed. Finally, the validity of the conclusions based on single amino acid mutations is examined.
Binding of phenol to R6 insulin hexamers.
Berchtold H, Hilgenfeld R
Biopolymers · 1999 · PMID 10397800 · Publisher ↗
Small amounts of phenolic compounds are being used as preservatives in pharmaceutical insulin preparations. It has been shown previously that these compounds bind to specific sites on the insulin hexamer and act as allos...
Small amounts of phenolic compounds are being used as preservatives in pharmaceutical insulin preparations. It has been shown previously that these compounds bind to specific sites on the insulin hexamer and act as allosteric effectors, inducing a transformation of the T6 hexamer to the R6 hexamer, via a T3R3 intermediate. In this article, the crystal structures of eight different insulin derivatives, all in the phenol-containing R6 form, are analyzed with respect to their phenol-binding sites. While six phenol molecules are normally bound per insulin hexamer, one of the engineered insulins appears to contain only three phenols but yet exists in an R6 conformation. This observation provides additional evidence for an inherent nonequivalence of the two trimers in the insulin hexamer. The unusual observation of a seventh phenol molecule bound to the hexamer of crystalline A21Gly-B31,B32Arg2 insulin (HOE 901), a long-acting derivative currently undergoing phase III clinical trials, provides a partial explanation for its protracted activity.
Novel RNA-binding motif: the KH module.
Adinolfi S, Bagni C, Castiglione Morelli MA … +3 more , Fraternali F, Musco G, Pastore A
Biopolymers · 1999 · PMID 10397799 · Publisher ↗
The KH motif has recently been identified in single or multiple copies in a number of RNA associated proteins. Here we review the current knowledge accumulated about the sequence, structure, and functions of the KH. The...
The KH motif has recently been identified in single or multiple copies in a number of RNA associated proteins. Here we review the current knowledge accumulated about the sequence, structure, and functions of the KH. The multidomain architecture of most of the KH-containing proteins inspired an approach based on the production of peptides spanning the sequence of an isolated KH motif. Correct identification of the minimal length necessary for producing a folded peptide has had a number of important consequences for interpreting functional data. The presence of the KH motifs in fmr1, the protein responsible for the fragile X syndrome, and their possible role in the fmr1 functions are also discussed.
Conformational analysis of peptide fragments derived from the peripheral subunit-binding domain from the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus: evidence for nonrandom structure in the unfolded state.
Spector S, Rosconi M, Raleigh DP
Biopolymers · 1999 Jan · PMID 10070261 · Publisher ↗
There is currently a great deal of interest in the early events in protein folding. Two issues that have generated particular interest are the nature of the unfolded state under native conditions and the role of local in...
There is currently a great deal of interest in the early events in protein folding. Two issues that have generated particular interest are the nature of the unfolded state under native conditions and the role of local interactions in folding. Here, we report the results of a study of a set of peptides derived from a small two-helix protein, the peripheral subunit-binding domain of the pyruvate dehydrogenase multienzyme complex. Five peptides of overlapping sequence were prepared, including sequences corresponding to each of the helices and to the region connecting them. The peptides were characterized by CD and, where possible, nmr. A peptide corresponding to the second helix is between 12 and 17% helical at neutral pH. CD also indicates a lower percentage of helical structure in the peptide corresponding to the first alpha-helix, although the values of the alpha-proton chemical shifts suggest some preference for nonrandom structure. Peptides corresponding to the interhelical loop, which in the full domain contains two overlapping beta-turns and a 5-residue 3(10)-helix, are less structured. There is no significant change in the helicity of any of these peptides with pH. To test for fragment complementation, CD spectra of the two peptides derived from each helix and the long connecting peptide were compared to the spectra of each possible pair, as well as to a mixture containing all three. No increase in structure was observed. We complement our peptide studies by characterizing a point mutant, D34V, which disrupts a critical hydrogen bonding network. This mutant is unable to fold and provides a useful model of the denatured state. The mutant is between 9 and 16% helical as judged by CD. The modest amount of helical structure formed in some of the peptide fragments and in the point mutant suggests that the denatured state of the peripheral subunit binding domain is not completely unstructured. This may contribute to the very rapid folding observed for the intact protein.
Rapid binding of a cationic active site inhibitor to wild type and mutant mouse acetylcholinesterase: Brownian dynamics simulation including diffusion in the active site gorge.
Tara S, Elcock AH, Kirchhoff PD … +4 more , Briggs JM, Radic Z, Taylor P, McCammon JA
Biopolymers · 1998 Dec · PMID 9838872 · Publisher ↗
It is known that anionic surface residues play a role in the long-range electrostatic attraction between acetylcholinesterase and cationic ligands. In our current investigation, we show that anionic residues also play an...
It is known that anionic surface residues play a role in the long-range electrostatic attraction between acetylcholinesterase and cationic ligands. In our current investigation, we show that anionic residues also play an important role in the behavior of the ligand within the active site gorge of acetylcholinesterase. Negatively charged residues near the gorge opening not only attract positively charged ligands from solution to the enzyme, but can also restrict the motion of the ligand once it is inside of the gorge. We use Brownian dynamics techniques to calculate the rate constant kon, for wild type and mutant acetylcholinesterase with a positively charged ligand. These calculations are performed by allowing the ligand to diffuse within the active site gorge. This is an extension of previously reported work in which a ligand was allowed to diffuse only to the enzyme surface. By setting the reaction criteria for the ligand closer to the active site, better agreement with experimental data is obtained. Although a number of residues influence the movement of the ligand within the gorge, Asp74 is shown to play a particularly important role in this function. Asp74 traps the ligand within the gorge, and in this way helps to ensure a reaction.
Src homology-2 domains: structure, mechanisms, and drug discovery.
Sawyer TK
Biopolymers · 1998 · PMID 9817027 · Publisher ↗
Src homology-2 (SH2) domains and their associated catalytic or noncatalytic proteins constitute critical signal transduction targets for drug discovery. Such SH2 proteins are found in the regulation of a number of cellul...
Src homology-2 (SH2) domains and their associated catalytic or noncatalytic proteins constitute critical signal transduction targets for drug discovery. Such SH2 proteins are found in the regulation of a number of cellular processes, including growth, mitogenesis, motility, metabolism, immune response, and gene transcription. From the relationship of tyrosine phosphorylation and intracellular regulation by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs), the dynamic and reversible binding interactions of SH2 domain containing proteins with their cognate phosphotyrosine (pTyr) containing proteins provide a third dimensionality to the orchestration of signal transduction pathways that exist as a result of pTyr formation, degradation, and molecular recognition events. This review highlights several key research achievements impacting our current understanding of SH2 structure, mechanisms, and drug discovery that underlie the role(s) of SH2 domains in signal transduction processes, cellular functions, and disease states.
Protein-tyrosine phosphatases: structure, mechanism, and inhibitor discovery.
Burke TR, Zhang ZY
Biopolymers · 1998 · PMID 9817026 · Publisher ↗
Protein-tyrosine kinases (PTKs) and their associated signaling pathways are crucial for the regulation of numerous cell functions including growth, mitogenesis, motility, cell-cell interactions, metabolism, gene transcri...
Protein-tyrosine kinases (PTKs) and their associated signaling pathways are crucial for the regulation of numerous cell functions including growth, mitogenesis, motility, cell-cell interactions, metabolism, gene transcription, and the immune response. Since tyrosine phosphorylation is reversible and dynamic in vivo, the phosphorylation states of proteins are governed by the opposing actions of PTKs and protein-tyrosine phosphatases (PTPs). In this light, both PTKs and PTPs play equally important roles in signal transduction in eukaryotic cells, and comprehension of mechanisms behind the reversible pTyr-dependent modulation of protein function and cell physiology must necessarily encompass the characterization of PTPs as well as PTKs. In spite of the large number of PTPs identified to date and the emerging role played by PTPs in disease, a detailed understanding of the role played by PTPs in signaling pathways has been hampered by the absence of PTP-specific agents. Such PTP-specific inhibitors could potentially serve as useful tools in determining the physiological significance of protein tyrosine phosphorylation in complex cellular signal transduction pathways and may constitute valuable therapeutics in the treatment of several human diseases. The goal of this review is therefore to summarize current understandings of PTP structure and mechanism of catalysis and the relationship of these to PTP inhibitor development. The review is organized such that enzyme structure is covered first, followed by mechanisms of catalysis then PTP inhibitor development. In discussing PTP inhibitor development, nonspecific inhibitors and those obtained by screening methods are initially presented with the focus then shifting to inhibitors that utilize a more structure-based rationale.
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