Abstract：
:Caspases are a family of aspartate-specific cysteine proteases that regulate cellular homeostasis through the mediation of apoptosis and inflammation. Despite keen interest in caspases as therapeutic targets for cancer, inflammatory, and neurodegenerative diseases, no active-site directed small molecule has yet succeeded in navigating human clinical trials. At the same time, recent biochemical and biophysical studies have revealed caspases to be highly dynamic proteases possessing a remarkable diversity of activation mechanisms. In addition, many caspases possess an allosteric circuit linking key active site loops with a distal allosteric site located at the dimer interface. Accordingly, small molecule binding at this allosteric site directly impacts structural organization of the active site and thus catalytic activity. Both cysteine-tethered and non-covalent reversible small molecules have recently been identified for these allosteric sites, with binding producing a variety of functional effects. Surprising new examples of caspase modulation have also been described recently, including a small molecule that binds caspase-6-substrate complexes uncompetitively and a short peptide that stabilizes an inactive, tetrameric form of procaspase-6. The confluence of recent biochemical, biophysical and pharmacological data has revealed exciting new avenues for the modulation of caspase activity via binding beyond the active site.
journal_name
Curr Opin Struct Bioljournal_title
Current opinion in structural biologyauthors
Murray J,Renslo ARdoi
10.1016/j.sbi.2013.10.002subject
Has Abstractpub_date
2013-12-01 00:00:00pages
812-9issue
6eissn
0959-440Xissn
1879-033Xpii
S0959-440X(13)00178-4journal_volume
23pub_type
杂志文章,评审abstract：:Akt1-3 (Akt) are a subset of the AGC protein Ser/Thr kinase family and play important roles in cell growth, metabolic regulation, cancer, and other diseases. We describe some of the roles of Akt in cell signaling and the biochemical and structural mechanisms of the regulation of Akt catalysis by the phospholipid PIP3 ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.02.004
更新日期：2019-12-01 00:00:00
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
更新日期：2012-06-01 00:00:00
abstract：:Advances in electron microscopes, detectors and data processing algorithms have greatly facilitated the structural determination of many challenging integral membrane proteins that have been evasive to crystallization. These breakthroughs facilitate the application and development of various membrane protein solubiliz...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.05.022
更新日期：2019-10-01 00:00:00
abstract：:Heparan sulfate (HS) is an essential and dynamic regulator of fibroblast growth factor (FGF) signaling. Two fundamentally different crystallographic models have been proposed to explain, at the molecular level, how HS/heparin enables FGF and FGF receptor (FGFR) to assemble into a functional dimer on the cell surface. ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2005.09.002
更新日期：2005-10-01 00:00:00
abstract：:Recent advances in algorithmic techniques and statistics of sequence alignment have helped to make near-optimal alignments an important tool in the delineation of biologically valid alignments. Near-optimal alignments serve to judge the reliability of portions of a sequence alignment. The statistical assessment of sub...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(96)80054-6
更新日期：1996-06-01 00:00:00
abstract：:Channel-forming bacterial toxins undergo a series of remarkable changes in solubility, oligomerization state, structure and dynamics during the processes of membrane binding, assembly, membrane insertion and channel formation. Recent high-resolution crystal structures of channel-forming toxins, in both water-soluble a...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(97)80123-6
更新日期：1997-08-01 00:00:00
abstract：:The past year has seen some major advances in the area of carbohydrate synthesis using chemical methods. Progress in all areas of synthetic methodology, including new protecting groups and coupling methods, has been reported. A number of complex carbohydrate structures have been prepared using known, as well as new, m...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(00)00252-9
更新日期：2001-10-01 00:00:00
abstract：:Electron cryo-microscopy (cryoEM) is used to determine structures of biological molecules, including multi-protein complexes. Maps at better than 3.0Å resolution are relatively straightforward to interpret since atomic models of proteins and nucleic acids can be built directly. Still, these resolutions are often diffi...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.06.009
更新日期：2019-10-01 00:00:00
abstract：:Functional conformational changes of proteins can facilitate numerous biological events in cells. The Markov state model (MSM) built from molecular dynamics simulations provide a powerful approach to study them. We here introduce a protocol that is tailor-made for constructing MSMs to study the functional conformation...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2020.10.005
更新日期：2020-10-27 00:00:00
abstract：:Telomerase is an RNP that synthesizes the 3' ends of linear chromosomes and is an important regulator of telomere length. It contains a single long non-coding telomerase RNA (TER), telomerase reverse transcriptase (TERT), and other proteins that vary among organisms. Recent progress in structural biology of telomerase...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2017.06.010
更新日期：2017-12-01 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：:Ising-like models have been remarkably successful in reproducing all the experimental data available on the equilibrium and kinetics of secondary structure formation in short peptides. Over the past two years, very similar models have been used to predict the folding of complete proteins, with encouraging results. Alt...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(00)00192-5
更新日期：2001-04-01 00:00:00
abstract：:Force spectroscopy has developed into an indispensable tool for studying folding and binding of proteins on a single molecule level in real time. Design of the pulling geometry allows tuning the reaction coordinate in a very precise manner. Many recent experiments have taken advantage of this possibility and have prov...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2012.11.007
更新日期：2013-02-01 00:00:00
abstract：:PUF proteins are RNA-binding proteins named for founding members PUMILIO and fem-3 binding factor (FBF). Together these proteins represent the range of known RNA recognition properties. PUMILIO is a prototypical PUF protein whose RNA sequence specificity is simple, elegant, and predictable. FBF displays differences in...
journal_title：Current opinion in structural biology
pub_type： 杂志文章
doi：10.1016/j.sbi.2008.12.009
更新日期：2009-02-01 00:00:00
abstract：:Optogenetic dimerizers are modular domains that can be utilized in a variety of versatile ways to modulate cellular biochemistry. Because of their modularity, many applications using these tools can be easily transferred to new targets without extensive engineering. While a number of photodimerizer systems are current...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.01.021
更新日期：2019-08-01 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：:The ISWI family of ATP-dependent chromatin remodelers regulates transcription of coding and noncoding RNA by mobilizing nucleosomes and controlling the length of linker DNA separating nucleosomes (spacing). Nucleosome movement is tightly coupled to the DNA translocation activity of the helicase domain in the catalytic...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2014.01.010
更新日期：2014-02-01 00:00:00
abstract：:Ribosomes translate genetic information encoded by mRNAs into protein chains with high fidelity. Truncated mRNAs lacking a stop codon will cause the synthesis of incomplete peptide chains and stall translating ribosomes. In bacteria, a ribonucleoprotein complex composed of tmRNA, a molecule that combines the functions...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2004.01.010
更新日期：2004-02-01 00:00:00
abstract：:The three-dimensional structures of several biotin-binding proteins are now known, giving insights into the molecular architecture of the binding sites for biotin. In combination with biochemical and computational approaches, these structural insights provide the basis for our present understanding of biotin-protein i...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(96)80010-8
更新日期：1996-12-01 00:00:00
abstract：:The anaphase-promoting complex/cyclosome (APC/C) is a large multi-subunit complex that functions as a RING domain E3 ubiquitin ligase to regulate transitions through the cell cycle, achieved by controlling the defined ubiquitin-dependent degradation of specific cell cycle regulators. APC/C activity and substrate selec...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.11.010
更新日期：2020-04-01 00:00:00
abstract：:Conformational changes are an essential feature of most molecular processes in biology. Optical tweezers have emerged as a powerful tool for probing conformational dynamics at the single-molecule level because of their high resolution and sensitivity, opening new windows on phenomena ranging from folding and ligand bi...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2015.06.006
更新日期：2015-10-01 00:00:00
abstract：:X-ray radiation damage to cryocooled ( approximately 100 K) macromolecular crystals has emerged as a general problem, especially since the advent of third generation synchrotron undulator sources. Interest in understanding the physical and chemical phenomena behind the observed effects is growing rapidly. The specific...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2006.08.001
更新日期：2006-10-01 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：:High-throughput interaction discovery initiatives have revealed the existence of hundreds of multiprotein complexes whose functions are regulated through thousands of protein-protein interactions (PPIs). However, the structural details of these interactions, often necessary to understand their function, are only avail...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2011.01.005
更新日期：2011-04-01 00:00:00
abstract：:Many proteins are composed of protein domains, functional units of common descent. Multidomain forms are common in all eukaryotes making up more than half of the proteome and the evolution of novel domain architecture has been accelerated in metazoans. It is also becoming increasingly clear that alternative splicing i...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.02.013
更新日期：2013-06-01 00:00:00
abstract：:The biological functions of protein molecules are intimately dependent on their conformational dynamics. This aspect is particularly evident for disordered proteins, which constitute perhaps one-third of the human proteome. Therefore, structural ensembles often offer more useful representations of proteins than indivi...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2016.12.004
更新日期：2017-02-01 00:00:00
abstract：:Structure-specific DNA nucleases play important roles in various DNA transactions such as DNA replication, repair and recombination. These enzymes recognize loops and branched DNA structures. Recent structural studies have provided detailed insights into the functions of these enzymes. Structures of Holliday junction ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2006.01.009
更新日期：2006-02-01 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：:Fundamental biological processes are driven by diverse molecular machineries. In recent years, single-molecule fluorescence spectroscopy has matured as a unique tool in biology to study how structural dynamics of molecular complexes drive various biochemical reactions. In this review, we highlight underlying developme...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.05.005
更新日期：2019-10-01 00:00:00
abstract：:Generally, non-catalytic carbohydrate binding module (CBM) specificity has been shown to parallel the catalytic activity of the carbohydrate active enzyme (CAZyme) module it is appended to. With the rapid expansion in metagenomic sequence space for the potential discovery of new CBMs in addition to the recent emergenc...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2014.07.004
更新日期：2014-10-01 00:00:00
