Abstract:
:Structural genomics (SG) has significantly increased the number of novel protein structures of targets with medical relevance. In the protein kinase area, SG has contributed >50% of all novel kinases structures during the past three years and determined more than 30 novel catalytic domain structures. Many of the released structures are inhibitor complexes and a number of them have identified new inhibitor binding modes and scaffolds. In addition, generated reagents, assays, and inhibitor screening data provide a diversity of chemogenomic data that can be utilized for early drug development. Here we discuss the currently available structural data for the kinase family considering novel structures as well as inhibitor complexes. Our analysis revealed that the structural coverage of many kinases families is still rather poor, and inhibitor complexes with diverse inhibitors are only available for a few kinases. However, we anticipate that with the current rate of structure determination and high throughput technologies developed by SG programs these gaps will be closed soon. In addition, the generated reagents will put SG initiatives in a unique position providing data beyond protein structure determination by identifying chemical probes, determining their binding modes and target specificity.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Marsden BD,Knapp Sdoi
10.1016/j.cbpa.2008.01.042subject
Has Abstractpub_date
2008-02-01 00:00:00pages
40-5issue
1eissn
1367-5931issn
1879-0402pii
S1367-5931(08)00025-2journal_volume
12pub_type
杂志文章,评审abstract::The atomic force microscope (AFM) allows biomolecules to be observed and manipulated under native conditions. It operates in buffer solution, produces molecular images with outstanding signal-to-noise ratio, and addresses single molecules. Progress in sample preparation and instrumentation has led to topographs that r...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2003.08.010
更新日期:2003-10-01 00:00:00
abstract::To transfer to the laboratory, the excellent efficiency shown by enzymes in Nature, biocatalysis, had to mimic several synthetic strategies used by the living organisms. Biosynthetic pathways are examples of tandem catalysis and may be assimilated in the biocatalysis field for the use of isolated multi-enzyme systems ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2013.02.015
更新日期:2013-04-01 00:00:00
abstract::The biochemical activities involved in signal transduction in cells are under tight spatiotemporal regulation. To study the effects of the spatial patterning and temporal dynamics of biochemical activities on downstream signaling, researchers require methods to manipulate signaling pathways acutely and rapidly. In thi...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2016.08.012
更新日期:2016-10-01 00:00:00
abstract::NMR, already some 50 years old, has long been an invaluable analytical method in industry for verification of chemical synthesis and compound characterisation. The range of molecular information accessible through NMR, however, offers a far larger horizon of applications. Of these, ligand screening by NMR has emerged ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(00)00204-0
更新日期:2001-06-01 00:00:00
abstract::Before large, specific peptides could be made, in an RNA world our ancestors may have used an RNA-like molecule for both catalysis and information storage. Taken together, RNA activities suggest RNA could have performed most of the essential informational functions of an ancient organism (i.e. those functions most sim...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/S1367-5931(99)80041-6
更新日期:1999-06-01 00:00:00
abstract::Covalent attachment of glycosylphosphatidylinositols (GPIs) to the protein C-terminus is one of the most common posttranslational modifications in eukaryotic cells. In addition to anchoring surface proteins to the cell membrane, GPIs also have many other important biological functions, determined by their unique struc...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2013.09.016
更新日期:2013-12-01 00:00:00
abstract::Recent studies of moonlighting functions and catalytic promiscuity provide insights into the structural and mechanistic bases of these phenomena. Moonlighting proteins that are highlighted include gephyrin, the Neurospora crassa tyrosyl tRNA synthetase, phosphoglucose isomerase, and cytochrome c. New insights into cat...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(03)00032-2
更新日期:2003-04-01 00:00:00
abstract::During 1996 and 1997, several chemical issues that arise in the early stages of preinitiation complex (PIC) formation were resolved. Kinetics experiments indicated that both TBP dimerization and DNA bending influence the rate of TBP-TATA box assembly. Affinity cleavage experiments indicated that TBP lacks the specific...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(98)80030-6
更新日期:1998-02-01 00:00:00
abstract::The introduction of fluorine atoms into organic molecules has received considerable attention as these organofluorines have often found widespread applications in bioorganic chemistry, medicinal chemistry and biomaterial science. Despite innovation of synthetic C-F forming methodologies, selective fluorination is stil...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2020.01.004
更新日期:2020-04-01 00:00:00
abstract::Chemical manipulation of natural, unengineered proteins is a daunting challenge which tests the limits of reaction design. By combining transition-metal or other catalysts with molecular recognition ideas, it is possible to achieve site-selective protein reactivity without the need for engineered recognition sequences...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2014.12.017
更新日期:2015-04-01 00:00:00
abstract::Fragment-based screening has now become an established method for the generation of lead molecules against therapeutic targets. Fragment molecules are simple, low molecular-weight compounds with few chemical functionalities. These characteristics lead to high hit rates for fragment screening as compared to the more cl...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2011.02.020
更新日期:2011-08-01 00:00:00
abstract::There is currently intense interest in unravelling the modus operandi of type I modular polyketide synthases in order to lay the ground work for their use in the combinatorial biosynthesis of new bioactive molecules. Much of our knowledge is derived from studies on 6-deoxyerythronolide B (DEBS), the enzyme assembling ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(99)00014-9
更新日期:1999-10-01 00:00:00
abstract::Although biotin and lipoic acid are two universally conserved cofactors essential for intermediary metabolism, their synthetic pathways have become known only in recent years. Both pathways have unusual features. Biotin synthesis in Escherichia coli requires a methylation that is later removed whereas lipoic acid is a...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2018.08.004
更新日期:2018-12-01 00:00:00
abstract::Small molecule production in microbial hosts is limited by the accumulation of the product inside the cell. Efflux transporters show promise as a solution to removal of the often-toxic products. Recent advances in transporter identification through expression profiling, heterologous expression, and knockout studies ha...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2015.05.019
更新日期:2015-10-01 00:00:00
abstract::Recently, the hypothesis that protein motions are involved in enzymatic turnover has gained significant attention. We review cases where there is evidence that protein motions are rate-limiting in the overall catalytic cycle and examine experimental and theoretical evidence for how such motions enhance the probability...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2010.07.020
更新日期:2010-10-01 00:00:00
abstract::The manufacture and use of protein microarrays with correctly folded and functional content presents significant challenges. Despite this, the feasibility and utility of such undertakings are now clear, and exciting progress has recently been demonstrated in the areas of content generation, printing strategies and pro...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2003.12.005
更新日期:2004-02-01 00:00:00
abstract::The broad utility of protein bioconjugates has created a need for new and diverse strategies for site-selective protein modification. In particular, chemical reactions that target alternative amino acid side chains or unnatural functional groups are emerging as a valuable complement to more commonly used lysine- and c...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2006.04.009
更新日期:2006-06-01 00:00:00
abstract::The oceans are filled with an amazing variety of biological materials including the glues and cements of mussels, barnacles, tube worms, algae, and starfish. Recent studies on mussel adhesive are providing increasing evidence for a unique mechanism of material generation involving iron-induced protein oxidation and cr...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2009.11.009
更新日期:2010-04-01 00:00:00
abstract::Oxidative cysteine modifications have emerged as a central mechanism for dynamic post-translational regulation of all major protein classes and correlate with many disease states. Elucidating the precise roles of cysteine oxidation in physiology and pathology presents a major challenge. This article reviews the curren...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2010.11.012
更新日期:2011-02-01 00:00:00
abstract::A broad range of biochemicals, from proteins to nucleic acids, function properly only when associated with a metal, usually a divalent cation. Not any divalent metal will do: these metals differ in their ionic radius, dissociation in water, ionization potential, and number of unpaired electrons in their outer shells, ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2018.09.017
更新日期:2019-04-01 00:00:00
abstract::Efficient library design is an ongoing challenge for investigators seeking novel ligands for proteins, whether for drug discovery or chemical biology. Strategies that add neglected chemistry or exclude unproductive compounds are two dominant recent themes, as is a growing awareness of molecular complexity and its impl...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2006.06.003
更新日期:2006-08-01 00:00:00
abstract::The past decade has seen rapid growth in the use of diverse compound libraries in classical phenotypic screens to identify modulators of a given process. The subsequent process of identifying the molecular targets of active hits, also called 'target deconvolution', is an essential step for understanding compound mecha...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2012.12.022
更新日期:2013-02-01 00:00:00
abstract::The function of nucleic acids has been an endless source of discovery and invention that has drastically enhanced our appreciation of DNA and RNA as multifaceted polymers. It is now widely known that nucleic acids can act as enzymes (deoxyribozymes and ribozymes) and as receptors (aptamers), and that these functional ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2006.04.003
更新日期:2006-06-01 00:00:00
abstract::The reactive oxygen and nitrogen species superoxide ion, nitric oxide, nitrogen dioxide and peroxynitrite ion all react with biological target molecules. Some of these interactions are carefully orchestrated segments of signal transduction cascades or part of the armamentarium of the immune system, others are patholog...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/S1367-5931(99)80036-2
更新日期:1999-04-01 00:00:00
abstract::Peptides that recognize specific cell types promise to be valuable tools both in research and clinical applications. Cell-specific peptides can be useful as drug delivery vehicles, diagnostic agents, affinity reagents for cell purification, gene therapy delivery agents, and research tools to probe the nature of a cell...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(99)00045-9
更新日期:2000-02-01 00:00:00
abstract::Nitrification is the aerobic process of the nitrogen cycle that converts ammonia to nitrate and is facilitated by ammonia-oxidizing and nitrite-oxidizing microorganisms. Ammonia-oxidizers are unique chemolithotrophs that evolved specialized networks of electron carriers to generate proton motive force using ammonia as...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2018.09.003
更新日期:2019-04-01 00:00:00
abstract::To improve the deconstruction of biomass, the most abundant terrestrial source of carbon polymers, en route to renewable fuels, chemicals, and materials more knowledge is needed into the mechanistic interplay between thermochemical pretreatment and enzymatic hydrolysis. In this review we highlight recent progress in a...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2015.08.014
更新日期:2015-12-01 00:00:00
abstract::Natural products continue to provide privileged scaffolds for drug discovery. However, challenges in supply and structure diversification can limit development. Here, we discuss recent (2017-2020) examples of synthetic biology approaches used to address challenges in supply and contribute to structure diversification ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2020.09.006
更新日期:2020-10-01 00:00:00
abstract::Some therapeutic monoclonal antibodies function by focusing the killing power of the immune system on particular cellular targets, a process known as antibody-dependent cell-mediated cytotoxicity (ADCC). There is considerable interest in developing small-molecule therapeutics that utilize this mechanism of action and ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2010.07.002
更新日期:2010-12-01 00:00:00
abstract::The nature of the oxidized halogen intermediate in vanadium bromoperoxidase has recently been shown to depend on the nature of the organic substrate. For example, in the presence of indoles, vanadium bromoperoxidase does not release a freely diffusible oxidized halogen intermediate (such as HOBr+/-BR2+/-Br3-). Regiose...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(98)80070-7
更新日期:1998-04-01 00:00:00