Abstract：
:Sugar nucleotide-modifying enzymes of the short-chain dehydrogenase/reductase type use transient oxidation-reduction by a tightly bound nicotinamide cofactor as a common strategy of catalysis to promote a diverse set of reactions, including decarboxylation, single- or double-site epimerization, and dehydration. Although the basic mechanistic principles have been worked out decades ago, the finely tuned control of reactivity and selectivity in several of these enzymes remains enigmatic. Recent evidence on uridine 5'-diphosphate (UDP)-glucuronic acid decarboxylases (UDP-xylose synthase, UDP-apiose/UDP-xylose synthase) and UDP-glucuronic acid-4-epimerase suggests that stereo-electronic constraints established at the enzyme's active site control the selectivity, and the timing of the catalytic reaction steps, in the conversion of the common substrate toward different products. The mechanistic idea of stereo-electronic control is extended to epimerases and dehydratases that deprotonate the Cα of the transient keto-hexose intermediate. The human guanosine 5'-diphosphate (GDP)-mannose 4,6-dehydratase was recently shown to use a minimal catalytic machinery, exactly as predicted earlier from theoretical considerations, for the β-elimination of water from the keto-hexose species.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Borg AJE,Beerens K,Pfeiffer M,Desmet T,Nidetzky Bdoi
10.1016/j.cbpa.2020.09.010subject
Has Abstractpub_date
2020-11-06 00:00:00pages
43-52eissn
1367-5931issn
1879-0402pii
S1367-5931(20)30132-0journal_volume
61pub_type
杂志文章,评审abstract：:Iron is an essential nutrient for life, and its capacity to cycle between different oxidation states is required for processes spanning oxygen transport and respiration to nucleotide synthesis and epigenetic regulation. However, this same redox ability also makes iron, if not regulated properly, a potentially dangerou...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.12.010
更新日期：2018-04-01 00:00:00
abstract：:Developing technologies such as unnatural amino acid mutagenesis, non-natural cofactor engineering, and computational design are generating proteins with novel functions; these proteins, however, often do not reach performance targets and would benefit from further optimization. Evolutionary methods can complement the...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2010.11.020
更新日期：2011-04-01 00:00:00
abstract：:Lysine acetylation has emerged as a key post-translational modification found at many sites throughout the cell. It plays an important role in epigenetic processes, and more generally in the regulation of protein stability and interactions. Acetyl groups are installed by lysine acetyltransferases and removed by lysine...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2018.06.015
更新日期：2018-08-01 00:00:00
abstract：:Recent structural information suggests that the HC(X)5R active-site motif defines three distinct evolutionary families of phosphatases that employ a common catalytic mechanism. In two instances, regulation of phosphatase activity employs autoinhibitory mechanisms involving either intermolecular or intramolecular inter...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(98)80095-1
更新日期：1998-10-01 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：:Study of protein adsorption to solid surfaces continues to be substantial because of its role in cellular responses to biomaterials, interest in molecular aspects such as conformation and orientation, new methods for making protein repellent surfaces, and new application areas such as nanoparticles and microfluidics. ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2011.04.016
更新日期：2011-10-01 00:00:00
abstract：:Lipopolysaccharide (LPS), a glycolipid found in the outer membrane of Gram-negative bacteria, is a potent elicitor of innate immune responses in mammals. A typical LPS molecule is composed of three different structural domains: a polysaccharide called the O-antigen, a core oligosaccharide, and Lipid A. Lipid A is the ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.07.008
更新日期：2017-10-01 00:00:00
abstract：:Metallodrugs are extensively used to treat and diagnose distinct disease types. The unique physical-chemical properties of metal ions offer tantalizing opportunities to tailor effective scaffolds for selectively targeting specific biomolecules. Modern experimental techniques have collected a large body of structural d...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.07.005
更新日期：2020-08-08 00:00:00
abstract：:The number of new chemical entities has remained rather constant (averaging 37 per year) in the past decade, despite the multiple-fold increase in the number of compounds that are being made and tested. Chemical space requires novel methods that can handle the increasing number of potentially accessible molecules. Nei...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00329-0
更新日期：2002-06-01 00:00:00
abstract：:Combinatorial chemistry methods and high-throughput screening for leads in industrial drug discovery have generated a potential bottleneck in the optimisation processes that seek to align potency with good pharmacokinetics in order to produce good medicines. This has resulted in the need for higher throughput methods ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章
doi：10.1016/s1367-5931(98)80017-3
更新日期：1998-06-01 00:00:00
abstract：:Fifty years after the publication of the DNA double helix model by Watson and Crick, new nucleic acid structures keep emerging at an ever-increasing rate. The past three years have brought a flurry of new oligonucleotide structures, including those of a Hoogsteen-paired DNA duplex, Holliday junctions, DNA-drug complex...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.09.004
更新日期：2004-12-01 00:00:00
abstract：:Protein citrullination is a post-translational modification of arginine that is catalyzed by the Protein Arginine Deiminase (PAD) family of enzymes. Aberrantly increased citrullination is associated with a host of inflammatory diseases and cancer and PAD inhibitors have shown remarkable efficacy in a range of diseases...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.10.014
更新日期：2016-02-01 00:00:00
abstract：:The notorious difficulty of elucidating structures of membrane transporters by crystallography has long prevented our understanding of active transport mechanism coupled with ion/proton transport. The determination of the first crystal structure of the drug/H+ antiporter AcrB was a breakthrough for structure-based und...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2003.08.014
更新日期：2003-10-01 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：:Chromatin organization spans a wide range of structural complexity. Substructures at the 10-200nm scale are poorly characterized, especially in living cells, due to the limitations of electron microscopy and standard optical microscopy. Recently developed super-resolution fluorescence microscopy methods represent an e...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2011.10.004
更新日期：2011-12-01 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：:Multicomponent reactions (MCRs) provide a powerful tool towards the one-pot synthesis of diverse and complex compounds on the one hand and small and 'drug-like' heterocycles on the other hand. No other single synthesis technology enables chemists to search such large chemical spaces as provided by MCRs. MCRs that invo...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00328-9
更新日期：2002-06-01 00:00:00
abstract：:Manganese, iron, copper, and zinc are observed to play essential roles in mitochondria. The overload and depletion of metal ions in mitochondria under pathological conditions, however, could disturb mitochondrial compartments and functions leading to cell death. In this review, we mainly summarize how impaired metal i...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.09.009
更新日期：2018-04-01 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：:Because biomarkers are typically low in abundance, the crucial step of biomarker discovery is to efficiently separate clinically relevant sets of proteins that might define disease stages and/or predict disease development. It is anticipated that a multi-dimensional fractionation system (MDFS) will provide an efficien...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2006.01.007
更新日期：2006-02-01 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：:Antibody-drug conjugates (ADCs) require multiple assays for analytical and bioanalytical characterization due to their heterogeneous and dynamic nature. These assays can help address questions from the drug-loading distribution following conjugation to exposure-response relationships after dosing in vivo. This review ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2013.03.022
更新日期：2013-06-01 00:00:00
abstract：:RNA plays an essential cellular role in nearly every aspect of the transmission and expression of genetic information, including regulatory roles that have significance for cellular development. Access to RNA bearing synthetic modifications has allowed biological chemists to probe deep into the inner workings of cellu...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2005.10.009
更新日期：2005-12-01 00:00:00
abstract：:The molecular mechanisms by which peptide antibiotics disrupt bacterial DNA synthesis, protein biosynthesis, cell wall biosynthesis, and membrane integrity are diverse, yet historically have been understood to follow a theme of one antibiotic, one inhibitory mechanism. In the past year, mechanistic and structural stud...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)00025-3
更新日期：1999-12-01 00:00:00
abstract：:Modular peptide synthetases, which act as the protein templates for the synthesis of a large number of peptide antibiotics and siderophores, hold great potential for the development of novel compounds. Recently, significant progress has been made towards understanding their molecular architecture and substrate specifi...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(97)80051-8
更新日期：1997-12-01 00:00:00
abstract：:Amide forming reactions are central to the field of peptide and protein synthesis and are considered to be poorly reversible reactions owing to the high stability of peptide bonds. One amide-forming reaction is native chemical ligation (NCL) which is driven by a sulfur to nitrogen acyl migration process from a transie...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2014.09.030
更新日期：2014-10-01 00:00:00
abstract：:Rapid progress in genomics and proteomics has provided a wealth of new targets for the pharmaceutical industry, even as many older targets still remain challenging for small-molecule drug discovery. Fragment-based lead discovery, in which leads are built progressively by expanding or combining small fragments, is a ra...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.06.010
更新日期：2004-08-01 00:00:00
abstract：:Recent advances in -omic profiling technologies have ushered in an era where we no longer want to merely measure the presence or absence of a biomolecule of interest, but instead hope to understand its function and interactions within larger signaling networks. Here, we review several emerging proteomic technologies c...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.02.001
更新日期：2020-02-01 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：:Peptide natural products (PNPs) represent a unique class of compounds known for their fascinating structural motifs with important biological activities. Lately, PNPs have garnered a lot of interest for their application in drug discovery. Nevertheless, lack of diversity oriented synthetic/biosynthetic platforms to ge...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.06.006
更新日期：2016-10-01 00:00:00
