Structure-based drug design.

Abstract:

:There are now many successful examples of the design of new ligands based on knowledge of target protein structures. In most cases those ligands are unsuitable as drugs because of problems of toxicity, stability or bioavailability. The past twelve months have also seen the description of the structures of many proteins which are either known to be targets for existing drugs or have clear potential to be utilized in therapy.

journal_name

Curr Opin Struct Biol

authors

Colman PM

doi

10.1016/0959-440x(94)90268-2

subject

Has Abstract

pub_date

1994-12-01 00:00:00

pages

868-74

issue

6

eissn

0959-440X

issn

1879-033X

pii

0959-440X(94)90268-2

journal_volume

4

pub_type

杂志文章,评审
  • Crystallization and structure determination of RNA.

    abstract::Progress in the synthesis, purification and crystallization of RNA has resulted in the determination of several X-ray crystal structures of RNA molecules over the past few years. Methods proven and under development will lead to future structure determinations and shed light on the structural basis for RNA's many func...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/0959-440x(95)80057-3

    authors: Lietzke SE,Barnes CL,Kundrot CE

    更新日期:1995-10-01 00:00:00

  • Gamma-tubulin complexes and their interaction with microtubule-organizing centers.

    abstract::Gamma-tubulin is as ubiquitous in eukaryotes as alpha- and beta-tubulin. Rather than forming part of the microtubule wall, however, gamma-tubulin is involved in microtubule nucleation. Although gamma-tubulin concentrates at microtubule-organizing centers, it also exists in a cytoplasmic complex whose size and complexi...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/S0959-440X(99)80035-9

    authors: Wiese C,Zheng Y

    更新日期:1999-04-01 00:00:00

  • Structural biology of DNA photolyases and cryptochromes.

    abstract::Photolyases repair cytotoxic and mutagenic UV-induced photolesions in DNA by using an amazing light-dependent repair mechanism. It involves light absorption, electron transfer from an excited reduced and deprotonated FADH(-) to the flipped-out photolesion, followed by the fragmentation of the photolesions. Cryptochrom...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2009.05.003

    authors: Müller M,Carell T

    更新日期:2009-06-01 00:00:00

  • Kinetic studies of beta-sheet protein folding.

    abstract::New studies have shown that folding of beta-sheet proteins can occur with and without intermediates, with fast to slow refolding rates and late to very late transition states. These experiments demonstrate that, despite early speculation to the contrary, beta-sheet protein folding does not appear to be fundamentally d...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/s0959-440x(98)80014-6

    authors: Capaldi AP,Radford SE

    更新日期:1998-02-01 00:00:00

  • Modulation of allosteric coupling by mutations: from protein dynamics and packing to altered native ensembles and function.

    abstract::A large body of work has gone into understanding the effect of mutations on protein structure and function. Conventional treatments have involved quantifying the change in stability, activity and relaxation rates of the mutants with respect to the wild-type protein. However, it is now becoming increasingly apparent th...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2018.09.004

    authors: Naganathan AN

    更新日期:2019-02-01 00:00:00

  • Characterizing transition states in protein folding: an essential step in the puzzle.

    abstract::Transition states in protein folding are being analyzed experimentally and by computer simulation to reveal the sequence of events in the folding and unfolding of proteins at high resolution. Results of this analysis have enabled the reconstruction of folding pathways in vitro and open the prospect of analyzing pathwa...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/0959-440x(95)80012-p

    authors: Fersht AR

    更新日期:1995-02-01 00:00:00

  • Evolution, folding, and design of TIM barrels and related proteins.

    abstract::Proteins are chief actors in life that perform a myriad of exquisite functions. This diversity has been enabled through the evolution and diversification of protein folds. Analysis of sequences and structures strongly suggest that numerous protein pieces have been reused as building blocks and propagated to many moder...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2020.12.007

    authors: Romero-Romero S,Kordes S,Michel F,Höcker B

    更新日期:2021-01-13 00:00:00

  • Aminoacyl-tRNA synthetases.

    abstract::Crystallographic studies of a number of aminoacyl-tRNA synthetases and their complexes with ATP, amino acid and cognate tRNA are leading to an increasingly detailed picture of how these sophisticated enzymes function. Within the two distinct structural classes of ten synthetases, many common features are apparent, alt...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/s0959-440x(97)80161-3

    authors: Cusack S

    更新日期:1997-12-01 00:00:00

  • Structural and physico-chemical effects of disease and non-disease nsSNPs on proteins.

    abstract::This review emphasizes the effects of naturally occurring mutations on structural features and physico-chemical properties of proteins. The basic protein characteristics considered are stability, dynamics, and the binding of proteins and methods for assessing effects of mutations on these macromolecular characteristic...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2015.01.003

    authors: Kucukkal TG,Petukh M,Li L,Alexov E

    更新日期:2015-06-01 00:00:00

  • Intermediate filament assembly: fibrillogenesis is driven by decisive dimer-dimer interactions.

    abstract::Intermediate filaments are built from one to several members of a multigene family encoding fibrous proteins that share a highly conserved hierarchic assembly plan for the formation of multistranded filaments from distinctly structured extended coiled coils. Despite the rather low primary sequence identity, intermedia...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/s0959-440x(98)80035-3

    authors: Herrmann H,Aebi U

    更新日期:1998-04-01 00:00:00

  • The use of neutron scattering to determine the functional structure of glycoside hydrolase.

    abstract::Neutron diffraction provides different information from X-ray diffraction, because neutrons are scattered by atomic nuclei, whereas X-rays are scattered by electrons. One of the key advantages of neutron crystallography is the ability to visualize hydrogen and deuterium atoms, making it possible to observe the protona...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2016.07.014

    authors: Nakamura A,Ishida T,Samejima M,Igarashi K

    更新日期:2016-10-01 00:00:00

  • A cradle for new proteins: trigger factor at the ribosome.

    abstract::Newly synthesized proteins leave the ribosome through a narrow tunnel in the large subunit. During ongoing synthesis, nascent protein chains are particularly sensitive to aggregation and degradation because they emerge from the ribosome in an unfolded state. In bacteria, the first protein to interact with nascent chai...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2005.03.005

    authors: Maier T,Ferbitz L,Deuerling E,Ban N

    更新日期:2005-04-01 00:00:00

  • A prokaryotic perspective on pentameric ligand-gated ion channel structure.

    abstract::The X-ray structures of two prokaryotic pentameric ligand-gated ion channels have recently provided detailed insight into this important family of neurotransmitter receptors. These prokaryotic homologs share the overall architecture of their eukaryotic counterparts with conservation in functionally important residues....

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2009.07.006

    authors: Hilf RJ,Dutzler R

    更新日期:2009-08-01 00:00:00

  • Eukaryotic translation initiation factors and regulators.

    abstract::Significant progress has been made over the past several years on structural studies of the eukaryotic translation initiation factors that facilitate the assembly of a translation-competent ribosome at the initiation codon of an mRNA. These structural studies have revealed the repeated use of a set of common structura...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/s0959-440x(03)00009-5

    authors: Sonenberg N,Dever TE

    更新日期:2003-02-01 00:00:00

  • New folds of plant lectins.

    abstract::Among the crystal structures of lectins determined recently, three--snowdrop lectin, jacalin and amaranthin--represent new lectin families. Their polypeptide folds share remarkably similar features and consist exclusively of beta structure. Autonomously folded beta-sheet subdomains, inter-related by a pseudothreefold ...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/s0959-440x(97)80071-1

    authors: Wright CS

    更新日期:1997-10-01 00:00:00

  • Molecular origins of binding affinity: seeking the Archimedean point.

    abstract::Connecting three dimensional structure and affinity is analogous to seeking the 'Archimedean point', a vantage point from where any observer can quantitatively perceive the subject of inquiry. Here we review current knowledge and challenges that lie ahead of us in the quest for this Archimedean point. We argue that cu...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2013.07.001

    authors: Kastritis PL,Bonvin AM

    更新日期:2013-12-01 00:00:00

  • Directly from the source: endogenous preparations of molecular machines.

    abstract::Purification from a source enriched in large macromolecular machines with basic cellular function is still the method of choice in many cases. Such complexes occur in sufficiently high copy numbers in the cell and can be isolated using classical protein purification protocols. Although advanced DNA recombinant technol...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2013.01.005

    authors: Mesa P,Deniaud A,Montoya G,Schaffitzel C

    更新日期:2013-06-01 00:00:00

  • Simulation of the structure and dynamics of nonhelical RNA motifs.

    abstract::Computer simulation methods are increasingly being used to study possible conformations and dynamics of structural motifs in RNA. Recent results of molecular dynamics simulations and continum solvent studies of RNA structures and RNA-ligand complexes show promising agreement with experimental data. Combined with the o...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章

    doi:10.1016/s0959-440x(00)00089-0

    authors: Zacharias M

    更新日期:2000-06-01 00:00:00

  • Exposing the kinetic traps in RNA folding.

    abstract::Large ribozymes fold on a 'glacial' timescale compared to the folding of their protein counterparts. The sluggish folding exhibited by large RNAs results from the formation of kinetically trapped, misfolded intermediates, which are nonessential features of the folding mechanism. Newly developed mutant ribozymes that a...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/S0959-440X(99)80045-1

    authors: Treiber DK,Williamson JR

    更新日期:1999-06-01 00:00:00

  • Beta propellers: structural rigidity and functional diversity.

    abstract::Recently solved structures and proposed models have helped to reveal the structural characteristics of the beta-propeller fold, as well as the features that contribute to its high rigidity and stability. Possible strategies for identifying beta-propeller proteins in newly characterised sequences are helping to overcom...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/s0959-440x(99)00035-4

    authors: Fülöp V,Jones DT

    更新日期:1999-12-01 00:00:00

  • Fast infrared spectroscopy of protein dynamics: advancing sensitivity and selectivity.

    abstract::2D-IR spectroscopy has matured to a powerful technique to study the structure and dynamics of peptides, but its extension to larger proteins is still in its infancy, the major limitations being sensitivity and selectivity. Site-selective information requires measuring single vibrational probes at sub-millimolar concen...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2015.03.012

    authors: Koziol KL,Johnson PJ,Stucki-Buchli B,Waldauer SA,Hamm P

    更新日期:2015-10-01 00:00:00

  • Molecular dynamics simulations of large macromolecular complexes.

    abstract::Connecting dynamics to structural data from diverse experimental sources, molecular dynamics simulations permit the exploration of biological phenomena in unparalleled detail. Advances in simulations are moving the atomic resolution descriptions of biological systems into the million-to-billion atom regime, in which n...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2015.03.007

    authors: Perilla JR,Goh BC,Cassidy CK,Liu B,Bernardi RC,Rudack T,Yu H,Wu Z,Schulten K

    更新日期:2015-04-01 00:00:00

  • Dynamics in multi-domain protein recognition of RNA.

    abstract::Protein-RNA interactions play essential roles in gene regulation and RNA metabolism. While high-resolution structures have revealed principles of RNA recognition by individual RNA binding domains (RBDs), the presence of multiple RBDs in many eukaryotic proteins suggests additional modes of RNA recognition by combinati...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2012.03.013

    authors: Mackereth CD,Sattler M

    更新日期:2012-06-01 00:00:00

  • Inhibiting protein-protein interactions using designed molecules.

    abstract::Continuing investigations into protein-protein interactions have revealed their key role in regulating a wide range of cellular processes. Although efforts to modulate these interactions are more challenging and much less mature than work on conventional drug discovery pathways, significant progress has been made on s...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2005.01.005

    authors: Zhao L,Chmielewski J

    更新日期:2005-02-01 00:00:00

  • Structure and function of the small ribozymes.

    abstract::Recently, major advances have been made toward increasing our understanding of small ribozyme structure and function. The first general acid-base catalytic mechanism for a ribozyme has been defined. Shifted nucleotide pK(a) values have been found to be surprisingly frequent structural elements. Finally, the dynamic na...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/s0959-440x(00)00207-4

    authors: Butcher SE

    更新日期:2001-06-01 00:00:00

  • The framework of polysaccharide monooxygenase structure and chemistry.

    abstract::Polysaccharide monooxygenases, or PMOs (also known as lytic PMOs or LPMOs), are a group of enzymes discovered in recent years to catalyze the oxidative degradation of carbohydrate polymers. The PMO catalytic domain has a β-sandwich fold that bears a strong resemblance to both immunoglobulin (Ig) and fibronectin type I...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2015.10.002

    authors: Span EA,Marletta MA

    更新日期:2015-12-01 00:00:00

  • Electrostatics calculations: latest methodological advances.

    abstract::Electrostatics plays a major role in the stabilization and function of biomolecules; as such, it remains a major focus of theoretical and computational studies of macromolecules. Electrostatic interactions are long range, and strongly dependent on the solvent and ions surrounding the biomolecule under study. During th...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2006.03.001

    authors: Koehl P

    更新日期:2006-04-01 00:00:00

  • Recognition at the cell surface: recent structural insights.

    abstract::In the past few years, structural biology has begun to reveal details of some of the receptors and associated interactions responsible for protein-mediated recognition events at the cell surface. Recent data span the fields of cytokine-receptor interactions, cell adhesion molecules and viral infection. ...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/0959-440x(95)80005-0

    authors: Stuart DI,Jones EY

    更新日期:1995-12-01 00:00:00

  • Controlling entropy to tune the functions of intrinsically disordered regions.

    abstract::Intrinsically disordered regions (IDRs) are fundamental units of protein function and regulation. Despite their inability to form a unique stable tertiary structure in isolation, many IDRs adopt a defined conformation upon binding and achieve their function through their interactions with other biomolecules. However, ...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2014.05.007

    authors: Flock T,Weatheritt RJ,Latysheva NS,Babu MM

    更新日期:2014-06-01 00:00:00

  • Probing RNA structure in vivo.

    abstract::RNA structure underpins many essential functions in biology. New chemical reagents and techniques for probing RNA structure in living cells have emerged in recent years. High-throughput, genome-wide techniques such as Structure-seq2 and DMS-MaPseq exploit nucleobase modification by dimethylsulfate (DMS) to obtain comp...

    journal_title:Current opinion in structural biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.sbi.2019.07.008

    authors: Mitchell D 3rd,Assmann SM,Bevilacqua PC

    更新日期:2019-12-01 00:00:00