Abstract:
:For various reasons, it seems sensible to redesign or design proteins from the inside out. Past approaches in this field have involved iterations of mutagenesis and characterisation to 'evolve' designs. Increasingly, combinatorial approaches are being taken to select 'fit' sequences from libraries of variant proteins. In particular, in silico methods have been used to good effect. More recently, experimental methods have been developed and improved. We are now in a position to redesign stability and function into natural protein frameworks confidently and to attempt de novo designs for more ambitious targets.
journal_name
Curr Opin Struct Bioljournal_title
Current opinion in structural biologyauthors
Woolfson DNdoi
10.1016/s0959-440x(00)00234-7subject
Has Abstractpub_date
2001-08-01 00:00:00pages
464-71issue
4eissn
0959-440Xissn
1879-033Xpii
S0959-440X(00)00234-7journal_volume
11pub_type
杂志文章,评审abstract::Investigating the in vitro refolding of proteins that naturally reside in biological membranes is a notoriously difficult task. Biophysical studies on model systems are beginning to provide a sound physical basis for membrane protein folding that should help to alleviate this problem. Highlights of these studies inclu...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/s0959-440x(99)80015-3
更新日期:1999-02-01 00:00:00
abstract::The protein folding problem can be viewed as three different problems: defining the thermodynamic folding code; devising a good computational structure prediction algorithm; and answering Levinthal's question regarding the kinetic mechanism of how proteins can fold so quickly. Once regarded as a grand challenge, prote...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2007.06.001
更新日期:2007-06-01 00:00:00
abstract::Progress in structural biology has begun to reveal the precise architecture of integral membrane proteins. However, the manner in which these complex structures are achieved remains unclear. Recent developments are starting to shed light on the unfolding and folding of a small but growing number of membrane proteins. ...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2006.06.004
更新日期:2006-08-01 00:00:00
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
更新日期:2019-02-01 00:00:00
abstract::Integrative structural modeling uses multiple types of input information and proceeds in four stages: (i) gathering information, (ii) designing model representation and converting information into a scoring function, (iii) sampling good-scoring models, and (iv) analyzing models and information. In the first stage, unc...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2014.08.001
更新日期:2014-10-01 00:00:00
abstract::Recent collection of high-resolution crystal structures of the 70S ribosome with mRNA and tRNA substrates enhances our knowledge of protein synthesis principles. A novel network of interactions between the ribosome in the elongation state and mRNA downstream from the A codon suggests that mRNA is stabilized and aligne...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2010.03.002
更新日期:2010-06-01 00:00:00
abstract::The structure of tubulin has recently been determined by electron crystallography, paving the way for a clearer understanding of the unique properties of tubulin that allow its varied functions within the cell. Some of the ongoing work on tubulin can be interpreted in terms of its structure, which can serve to guide f...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/s0959-440x(98)80099-7
更新日期:1998-12-01 00:00:00
abstract::C-type lectins are the largest and most diverse family of mammalian carbohydrate-binding proteins. They share a common protein fold, which provides the unifying basis for calcium-mediated carbohydrate recognition. Their involvement in a multitude of biological functions is remarkable. Here, we review the variety of ta...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2019.11.003
更新日期:2020-06-01 00:00:00
abstract::Biology has, and continues to be, shaped by evolutionary mechanisms. Within the past decade, local fitness landscapes have become experimentally tractable and are providing new perspectives on evolutionary mechanisms. Powered by next-generation sequencing, the impacts of all individual amino acid substitutions on func...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2018.01.001
更新日期:2018-02-01 00:00:00
abstract::Zinc finger proteins are among the most abundant proteins in eukaryotic genomes. Their functions are extraordinarily diverse and include DNA recognition, RNA packaging, transcriptional activation, regulation of apoptosis, protein folding and assembly, and lipid binding. Zinc finger structures are as diverse as their f...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/s0959-440x(00)00167-6
更新日期:2001-02-01 00:00:00
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 protein...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/0959-440x(94)90268-2
更新日期:1994-12-01 00:00:00
abstract::Molecular dynamics simulation studies of protein-nucleic acid complexes are more complicated than studies of either component alone-the force field has to be properly balanced, the systems tend to become very large, and a careful treatment of solvent and of electrostatic interactions is necessary. Recent investigation...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2007.12.012
更新日期:2008-04-01 00:00:00
abstract::The structure of the visual pigment rhodopsin in the dark state was first investigated by electron microscopy (EM). More recently, rhodopsin has been crystallised in two different space groups--a tetragonal P4(1) crystal form and a trigonal P3(1) packing arrangement. The structures of the pigment, determined by X-ray ...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2005.07.010
更新日期:2005-08-01 00:00:00
abstract::O-GlcNAcylation is an enzymatic post-translational modification occurring in hundreds of protein substrates. This modification occurs through the addition of the monosaccharide N-acetylglucosamine to serine and threonine residues on intracellular proteins in the cytosol, nucleus, and mitochondria. As a highly dynamic ...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2020.12.005
更新日期:2021-01-09 00:00:00
abstract::NMR relaxation experiments of isotopically labeled proteins provide a wealth of information on reorientational global and local dynamics on nanosecond and subnanosecond timescales for folded and nonfolded proteins in solution. Recent methodological advances in the interpretation of relaxation data have led to a better...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/s0959-440x(03)00036-8
更新日期:2003-04-01 00:00:00
abstract::The surfaces of all microbes are 'sugar coated' with molecules such as lipopolysaccharides in Gram-negative bacteria, capsular polysaccharides in bacteria, lipoarabinomannans in mycobacteria and lipophosphoglycan in Leishmania. The basic structures of these glycoconjugates are known and, in the case of pathogens, they...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/s0959-440x(98)80146-2
更新日期:1998-10-01 00:00:00
abstract::ATP synthases are rotary enzymes found in bacteria, chloroplasts, and mitochondria. These complexes produce the majority of cellular ATP in aerobic cells using energy from the transmembrane proton motive force established by the electron transport chain. In mitochondria, dimeric ATP synthase is essential for formation...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2018.08.005
更新日期:2018-10-01 00:00:00
abstract::The Jumonji-C (JmjC) subfamily of 2-oxoglutarate (2OG)-dependent oxygenases are of biomedical interest because of their roles in the regulation of gene expression and protein biosynthesis. Human JmjC 2OG oxygenases catalyze oxidative modifications to give either chemically stable alcohol products, or in the case of Nɛ...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2016.05.013
更新日期:2016-12-01 00:00:00
abstract::Recently, advances have been made in methods and applications that integrate electron microscopy density maps and comparative modeling to produce atomic structures of macromolecular assemblies. Electron microscopy can benefit from comparative modeling through the fitting of comparative models into electron microscopy ...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2005.08.001
更新日期:2005-10-01 00:00:00
abstract::The encounter complex of two proteins is a dynamic intermediate state that guides proteins to their binding site, thus enhancing the rate of complex formation. It is particularly useful for complexes that must balance a biological requirement for high turnover with the need for specific binding, such as electron trans...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2013.07.009
更新日期:2013-12-01 00:00:00
abstract::Protein biogenesis integrates multiple finely regulated mechanisms, ensuring nascent polypeptide chains are correctly enzymatically processed, targeted to membranes and folded to native structure. Recent studies show that the cellular translation machinery serves as hub that coordinates the maturation events in space ...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2013.11.004
更新日期:2014-02-01 00:00:00
abstract::The ClC proteins are members of a large family of chloride transport proteins, which are involved in a variety of physiological processes. All family members share a conserved molecular architecture consisting of a complex transmembrane transport domain and a soluble regulatory domain. To date, representative structur...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2006.06.002
更新日期:2006-08-01 00:00:00
abstract::There has been significant recent progress in the computational design of protein interactions including the creation of novel heterodimers, homodimers, nanohedra, fibril caps and a protein crystal. Essential to these successes has been the use of innovative strategies for finding binding modes that are achievable, th...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2013.04.010
更新日期:2013-08-01 00:00:00
abstract::Protein scientists are paving the way to a new phase in protein design and engineering. Approaches and methods are being developed that could allow the design of proteins beyond the confines of natural protein structures. This possibility of designing entirely new proteins opens new questions: What do we build? How do...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2015.05.009
更新日期:2015-08-01 00:00:00
abstract::Intrinsically disordered proteins (IDPs) are increasingly realized to play diverse biological roles, ranging from molecular signaling to the formation of membraneless organelles. Their high degree of disorder makes them more challenging to study using the techniques of conventional structural biology, because any obse...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2017.01.006
更新日期:2017-02-01 00:00:00
abstract::Current knowledge about the determinants of beta-sheet formation has been notably improved by the structural and kinetic analysis of model peptides, by mutagenesis experiments in proteins and by the statistical analysis of the protein structure database (Protein Data Bank; PDB). In the past year, several peptides comp...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/s0959-440x(99)80069-4
更新日期:1999-08-01 00:00:00
abstract::In all contemporary organisms, the active site of the ribosome--the peptidyl transferase center--catalyzes two distinct reactions, peptide bond formation between peptidyl-tRNA and aminoacyl-tRNA as well as the hydrolysis of peptidyl-tRNA with the help of a release factor. However, when provided with appropriate substr...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2013.04.012
更新日期:2013-08-01 00:00:00
abstract::Transmembrane proton gradients, known as Proton Motive Force (PMF), serve important physiological functions. In addition to driving ATP synthesis, PMF is harnessed by a large variety of secondary transporters to achieve 'uphill' translocation of specific substrates across the membrane. Proton-coupled secondary transpo...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2013.04.011
更新日期:2013-08-01 00:00:00
abstract::The wide occurrence of sialic acids (Sia) in various chemical forms linked as monomers or polymers in an outstanding position in a multitude of complex carbohydrates of animals and microorganisms renders them as most versatile function modulators in cell biology and pathology. A survey is presented of recent advances ...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2009.06.003
更新日期:2009-10-01 00:00:00
abstract::The modulation of enzyme function is a key regulatory feature of biological systems. The ability to engineer synthetic enzymes that can be controlled by any arbitrary signal would enable a wide array of sensing applications and therapeutics and provide us with powerful tools for the basic study of biology. Here severa...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2009.04.007
更新日期:2009-08-01 00:00:00