Abstract：
:Enzymes are nature's powerful catalytic proteins to perform reactions with often outstanding activity, selectivity and specificity. Moreover, the access to non-natural functions of biocatalysts can be facilitated by enzyme engineering. While rational approaches are often focused on an enzyme's active site, from random directed evolution we know that further functional hotspots must exist beyond the active site. Addressing flexible structural elements of these biocatalysts like loops and channels in enzyme engineering has the potential to fill this knowledge gap. The structural dynamics of enzyme catalysts are vital to promote their remarkable functions. This influences for example the access, recognition and orientation of substrates. Herein, we review recent examples of loop and channel engineering and classify them according to their use of simulation methodologies, predictions prior to engineering, the engineering methodologies themselves and discoveries found after the engineering. Thereby we highlight current possibilities and make suggestions to further unlock the potential of this yet underexplored strategy.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Kreß N,Halder JM,Rapp LR,Hauer Bdoi
10.1016/j.cbpa.2018.09.010subject
Has Abstractpub_date
2018-12-01 00:00:00pages
109-116eissn
1367-5931issn
1879-0402pii
S1367-5931(18)30039-5journal_volume
47pub_type
杂志文章,评审abstract：:Oligosaccharyl transferase is part of the macromolecular machinery that processes nascent proteins in the endoplasmic reticulum. The enzyme is highly conserved, catalyzes the initial step in the biosynthesis of N-linked glycoproteins and acts as a 'gatekeeper' for the secretory pathway. As more proteins associated wit...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00390-3
更新日期：2002-12-01 00:00:00
abstract：:Metabolomics and lipidomics aim to comprehensively measure the dynamic changes of all metabolites and lipids that are present in biological systems. The use of ion mobility-mass spectrometry (IM-MS) for metabolomics and lipidomics has facilitated the separation and the identification of metabolites and lipids in compl...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.10.033
更新日期：2018-02-01 00:00:00
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：:Metabolic oligosaccharide engineering and chemoenzymatic glycan labeling have provided powerful tools to study glycans in living systems and tissue samples. In this review article, we summarize recent advances in this field with a focus on innovative approaches for glycan imaging. The presented applications demonstrat...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.04.018
更新日期：2017-08-01 00:00:00
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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：:New insights have been gained into the therapeutic relevance of the sphingosine 1-phosphate (S1P) pathway, on the basis of reverse pharmacological approaches to defining the mechanism of action of the immunosuppressive agent FTY720. Natural and synthetic sphingosine 1-phosphate receptor agonists can make picomolar int...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(03)00085-1
更新日期：2003-08-01 00:00:00
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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：:Lipids are a vital class of molecules that play important and varied roles in biological processes, however, fully understanding these roles is extremely difficult due to the immense number and diversity of possible lipid species. While recent advances in chromatography and high resolution mass spectrometry have great...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.11.009
更新日期：2018-02-01 00:00:00
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journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)00058-7
更新日期：2000-02-01 00:00:00
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journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.05.014
更新日期：2017-10-01 00:00:00
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journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)80024-6
更新日期：1999-04-01 00:00:00
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journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2009.08.016
更新日期：2009-12-01 00:00:00
abstract：:There has been a significant increase in the number of compounds synthesized in early drug-discovery programs with the advances in combinatorial chemistry and high-throughput biological screening efforts. Various in silico, in vitro and in situ approaches have been described in literature that achieve higher throughpu...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00228-3
更新日期：2001-08-01 00:00:00
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journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2014.10.021
更新日期：2015-02-01 00:00:00
abstract：:Protein engineering over the past four years has made rhodopsin-based genetically encoded voltage indicators a leading candidate to achieve the task of reporting action potentials from a population of genetically targeted neurons in vivo. Rational design and large-scale screening efforts have steadily improved the dyn...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.05.006
更新日期：2015-08-01 00:00:00
abstract：:Recent advances in multidimensional nuclear magnetic resonance methodology to obtain 1H, 15N and 13C resonance assignments, interproton distance and torsion angle restraints, and restraints that characterize long-range order, coupled with new methods of structure refinement and novel methods for reducing linewidths, h...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(98)80084-7
更新日期：1998-10-01 00:00:00
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journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2010.02.018
更新日期：2010-06-01 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：:Initiating and terminating free-radical reactionis via hydrogen atom transfer (HAT) is an attractive means of avoiding substrate prefunctionalization. Small molecule catalysts and reagents, however, struggle to execute this fundamental step with useful levels of diastereoselectivity and enantioselectivity. In contrast...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2018.09.001
更新日期：2019-04-01 00:00:00
abstract：:The principles of enzyme chemistry, mechanism of action and inhibitor design are being applied to proteomics by the development of activity-based probes. This approach suggests a potentially broad method for interrogating enzyme family members, both known and unknown, in cells and proteomic fractions without the need ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00013-3
更新日期：2003-02-01 00:00:00
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journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.01.019
更新日期：2017-04-01 00:00:00
abstract：:Natural enzymes that catalyze Diels-Alder reactions have long been sought after, yet few enzymes have been experimentally confirmed to perform this reaction. In the past five years, several stand-alone enzymes that can catalyze the Diels-Alder reaction had been identified and characterized. Among which, the crystal st...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.09.015
更新日期：2016-12-01 00:00:00
abstract：:Conceptual and computational advances triggered an explosion of designed protein structures in the recent years. Various protein fold geometries have been robustly designed with atomic accuracy, including protein folds unseen in nature. The same principles and tools have been extended to design multi-chain assemblies....
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.06.020
更新日期：2017-10-01 00:00:00
abstract：:Given the correlation between many human diseases and mis-regulated transcription, there is a growing need for molecules that can inhibit or mimic key interactions between transcriptional activators and their binding partners. Because transcriptional activators typically participate in many different protein-protein b...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2005.08.012
更新日期：2005-10-01 00:00:00
abstract：:The asymmetric bioreduction of alkenes bearing an electron-withdrawing group using flavin-dependent enzymes from the 'old yellow enzyme' family at the expense of NAD(P)H yields the corresponding non-racemic alkanes going in hand with the creation of up to two chiral carbon centres. To avoid external cofactor recycling...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2007.02.025
更新日期：2007-04-01 00:00:00
abstract：:Recent advances in the development of the phosphorescent Ir(III) complexes have made it possible to implement the phosphorescence modality in bioimaging applications. A variety of phosphorescent Ir(III) complexes have been synthesized and assessed in the context of in vitro and in vivo imaging, especially in subcellul...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2013.05.023
更新日期：2013-08-01 00:00:00
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：:Single nucleotide polymorphism (SNP) genotyping has become a key technology for genetic studies. In recent years, matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry has emerged as a very powerful method for SNP genotyping. Here, we discuss our experience in implementing a high-through...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(01)00290-3
更新日期：2002-02-01 00:00:00
abstract：:Structural modification of naturally occurring beta-lactams and beta-lactones is a highly effective strategy for generating drugs for treating bacterial infections, cancer, obesity, and hyperlipidemia. These drugs acylate catalytic amino acids (serine, threonine, or cysteine) in enzyme targets such as penicillin-bindi...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2010.03.035
更新日期：2010-06-01 00:00:00
abstract：:Oligonucleotide in vitro selection provides surprisingly specific aptamers to protein targets. Synthetic chemistries for modifying nucleotides have been developed to enhance aptamer binding affinity. The diversity of nucleosides amenable to either triphosphate synthesis or phosphoramidite activation is now sufficientl...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(97)80103-2
更新日期：1997-06-01 00:00:00
