LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 193

Search options

  1. Article ; Online: The evolution and engineering of enzyme activity through tuning conformational landscapes.

    Damry, Adam M / Jackson, Colin J

    Protein engineering, design & selection : PEDS

    2021  Volume 34

    Abstract: Proteins are dynamic molecules whose structures consist of an ensemble of conformational states. Dynamics contribute to protein function and a link to protein evolution has begun to emerge. This increased appreciation for the evolutionary impact of ... ...

    Abstract Proteins are dynamic molecules whose structures consist of an ensemble of conformational states. Dynamics contribute to protein function and a link to protein evolution has begun to emerge. This increased appreciation for the evolutionary impact of conformational sampling has grown from our developing structural biology capabilities and the exploration of directed evolution approaches, which have allowed evolutionary trajectories to be mapped. Recent studies have provided empirical examples of how proteins can evolve via conformational landscape alterations. Moreover, minor conformational substates have been shown to be involved in the emergence of new enzyme functions as they can become enriched through evolution. The role of remote mutations in stabilizing new active site geometries has also granted insight into the molecular basis underpinning poorly understood epistatic effects that guide protein evolution. Finally, we discuss how the growth of our understanding of remote mutations is beginning to refine our approach to engineering enzymes.
    MeSH term(s) Catalytic Domain ; Evolution, Molecular ; Mutation ; Protein Conformation ; Proteins/genetics
    Chemical Substances Proteins
    Language English
    Publishing date 2021-03-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1466729-0
    ISSN 1741-0134 ; 1741-0126
    ISSN (online) 1741-0134
    ISSN 1741-0126
    DOI 10.1093/protein/gzab009
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Identification and Characterization of a Bacterial Periplasmic Solute Binding Protein That Binds l-Amino Acid Amides.

    Smith, Oliver B / Frkic, Rebecca L / Rahman, Marina G / Jackson, Colin J / Kaczmarski, Joe A

    Biochemistry

    2024  

    Abstract: Periplasmic solute-binding proteins (SBPs) are key ligand recognition components of bacterial ATP-binding cassette (ABC) transporters that allow bacteria to import nutrients and metabolic precursors from the environment. Periplasmic SBPs comprise a large ...

    Abstract Periplasmic solute-binding proteins (SBPs) are key ligand recognition components of bacterial ATP-binding cassette (ABC) transporters that allow bacteria to import nutrients and metabolic precursors from the environment. Periplasmic SBPs comprise a large and diverse family of proteins, of which only a small number have been empirically characterized. In this work, we identify a set of 610 unique uncharacterized proteins within the SBP_bac_5 family that are found in conserved operons comprising genes encoding (i) ABC transport systems and (ii) putative amidases from the FmdA_AmdA family. From these uncharacterized SBP_bac_5 proteins, we characterize a representative periplasmic SBP from
    Language English
    Publishing date 2024-05-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1108-3
    ISSN 1520-4995 ; 0006-2960
    ISSN (online) 1520-4995
    ISSN 0006-2960
    DOI 10.1021/acs.biochem.4c00096
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 217: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Evo-velocity: Protein language modeling accelerates the study of evolution.

    Sandhu, Mahakaran / Spence, Matthew A / Jackson, Colin J

    Cell systems

    2022  Volume 13, Issue 4, Page(s) 271–273

    Abstract: Understanding how protein sequences have evolved is one of the defining challenges in modern biology. In this issue of Cell Systems, Hie et al. describe a novel phylogenetic approach, dubbed "evo-velocity," that exploits protein language modeling to ... ...

    Abstract Understanding how protein sequences have evolved is one of the defining challenges in modern biology. In this issue of Cell Systems, Hie et al. describe a novel phylogenetic approach, dubbed "evo-velocity," that exploits protein language modeling to overcome many limitations of traditional phylogenetic analysis.
    MeSH term(s) Biological Evolution ; Language ; Phylogeny
    Language English
    Publishing date 2022-04-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2854138-8
    ISSN 2405-4720 ; 2405-4712
    ISSN (online) 2405-4720
    ISSN 2405-4712
    DOI 10.1016/j.cels.2022.03.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Asymmetric Ene-Reduction by F

    Kang, Suk Woo / Antoney, James / Lupton, David W / Speight, Robert / Scott, Colin / Jackson, Colin J

    Chembiochem : a European journal of chemical biology

    2023  Volume 24, Issue 8, Page(s) e202200797

    Abstract: Asymmetric reduction by ene-reductases has received considerable attention in recent decades. While several enzyme families possess ene-reductase activity, the Old Yellow Enzyme (OYE) family has received the most scientific and industrial attention. ... ...

    Abstract Asymmetric reduction by ene-reductases has received considerable attention in recent decades. While several enzyme families possess ene-reductase activity, the Old Yellow Enzyme (OYE) family has received the most scientific and industrial attention. However, there is a limited substrate range and few stereocomplementary pairs of current ene-reductases, necessitating the development of a complementary class. Flavin/deazaflavin oxidoreductases (FDORs) that use the uncommon cofactor F
    MeSH term(s) Oxidoreductases/metabolism ; Mycobacterium smegmatis ; Riboflavin/metabolism ; NADPH Dehydrogenase/chemistry ; Biocatalysis ; Oxidation-Reduction
    Chemical Substances Oxidoreductases (EC 1.-) ; factor 420 (37333-48-5) ; Riboflavin (TLM2976OFR) ; NADPH Dehydrogenase (EC 1.6.99.1)
    Language English
    Publishing date 2023-03-08
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020469-3
    ISSN 1439-7633 ; 1439-4227
    ISSN (online) 1439-7633
    ISSN 1439-4227
    DOI 10.1002/cbic.202200797
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Computational design and experimental characterisation of a stable human heparanase variant.

    Whitefield, Cassidy / Hong, Nansook / Mitchell, Joshua A / Jackson, Colin J

    RSC chemical biology

    2022  Volume 3, Issue 3, Page(s) 341–349

    Abstract: Heparanase is the only human enzyme known to hydrolyse heparin sulfate and is involved in many important physiological processes. However, it is also unregulated in many disease states, such as cancer, diabetes and Covid-19. It is thus an important drug ... ...

    Abstract Heparanase is the only human enzyme known to hydrolyse heparin sulfate and is involved in many important physiological processes. However, it is also unregulated in many disease states, such as cancer, diabetes and Covid-19. It is thus an important drug target, yet the heterologous production of heparanase is challenging and only possible in mammalian or insect expression systems, which limits the ability of many laboratories to study it. Here we describe the computational redesign of heparanase to allow high yield expression in
    Language English
    Publishing date 2022-02-15
    Publishing country England
    Document type Journal Article
    ISSN 2633-0679
    ISSN (online) 2633-0679
    DOI 10.1039/d1cb00239b
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: The role of oligomerization in the optimization of cyclohexadienyl dehydratase conformational dynamics and catalytic activity.

    East, Nicholas J / Clifton, Ben E / Jackson, Colin J / Kaczmarski, Joe A

    Protein science : a publication of the Protein Society

    2022  Volume 31, Issue 12, Page(s) e4510

    Abstract: The emergence of oligomers is common during the evolution and diversification of protein families, yet the selective advantage of oligomerization is often cryptic or unclear. Oligomerization can involve the formation of isologous head-to-head interfaces ( ...

    Abstract The emergence of oligomers is common during the evolution and diversification of protein families, yet the selective advantage of oligomerization is often cryptic or unclear. Oligomerization can involve the formation of isologous head-to-head interfaces (e.g., in symmetrical dimers) or heterologous head-to-tail interfaces (e.g., in cyclic complexes), the latter of which is less well studied and understood. In this work, we retrace the emergence of the trimeric form of cyclohexadienyl dehydratase from Pseudomonas aeruginosa (PaCDT) by introducing residues that form the PaCDT trimer-interfaces into AncCDT-5 (a monomeric reconstructed ancestor of PaCDT). We find that single interface mutations can switch the oligomeric state of the variants and that trimerization corresponds with a reduction in the K
    MeSH term(s) Prephenate Dehydratase/chemistry ; Prephenate Dehydratase/genetics ; Prephenate Dehydratase/metabolism ; Molecular Dynamics Simulation ; Pseudomonas aeruginosa ; Molecular Conformation ; Protein Multimerization
    Chemical Substances cyclohexadienyl dehydratase (EC 4.2.1.-) ; Prephenate Dehydratase (EC 4.2.1.51)
    Language English
    Publishing date 2022-11-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1106283-6
    ISSN 1469-896X ; 0961-8368
    ISSN (online) 1469-896X
    ISSN 0961-8368
    DOI 10.1002/pro.4510
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3407: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 1: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: Mononuclear binding and catalytic activity of europium(III) and gadolinium(III) at the active site of the model metalloenzyme phosphotriesterase.

    Breeze, Callum W / Nakano, Yuji / Campbell, Eleanor C / Frkic, Rebecca L / Lupton, David W / Jackson, Colin J

    Acta crystallographica. Section D, Structural biology

    2024  Volume 80, Issue Pt 4, Page(s) 289–298

    Abstract: Lanthanide ions have ideal chemical properties for catalysis, such as hard Lewis acidity, fast ligand-exchange kinetics, high coordination-number preferences and low geometric requirements for coordination. As a result, many small-molecule lanthanide ... ...

    Abstract Lanthanide ions have ideal chemical properties for catalysis, such as hard Lewis acidity, fast ligand-exchange kinetics, high coordination-number preferences and low geometric requirements for coordination. As a result, many small-molecule lanthanide catalysts have been described in the literature. Yet, despite the ability of enzymes to catalyse highly stereoselective reactions under gentle conditions, very few lanthanoenzymes have been investigated. In this work, the mononuclear binding of europium(III) and gadolinium(III) to the active site of a mutant of the model enzyme phosphotriesterase are described using X-ray crystallography at 1.78 and 1.61 Å resolution, respectively. It is also shown that despite coordinating a single non-natural metal cation, the PTE-R18 mutant is still able to maintain esterase activity.
    MeSH term(s) Phosphoric Triester Hydrolases/chemistry ; Phosphoric Triester Hydrolases/metabolism ; Catalytic Domain ; Gadolinium ; Europium ; Lanthanoid Series Elements ; Cations ; Metalloproteins
    Chemical Substances Phosphoric Triester Hydrolases (EC 3.1.8.-) ; Gadolinium (AU0V1LM3JT) ; Europium (444W947O8O) ; Lanthanoid Series Elements ; Cations ; Metalloproteins
    Language English
    Publishing date 2024-03-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2968623-4
    ISSN 2059-7983 ; 0907-4449
    ISSN (online) 2059-7983
    ISSN 0907-4449
    DOI 10.1107/S2059798324002316
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article ; Online: Rugged fitness landscapes minimize promiscuity in the evolution of transcriptional repressors.

    Meger, Anthony T / Spence, Matthew A / Sandhu, Mahakaran / Matthews, Dana / Chen, Jackie / Jackson, Colin J / Raman, Srivatsan

    Cell systems

    2024  Volume 15, Issue 4, Page(s) 374–387.e6

    Abstract: How a protein's function influences the shape of its fitness landscape, smooth or rugged, is a fundamental question in evolutionary biochemistry. Smooth landscapes arise when incremental mutational steps lead to a progressive change in function, as ... ...

    Abstract How a protein's function influences the shape of its fitness landscape, smooth or rugged, is a fundamental question in evolutionary biochemistry. Smooth landscapes arise when incremental mutational steps lead to a progressive change in function, as commonly seen in enzymes and binding proteins. On the other hand, rugged landscapes are poorly understood because of the inherent unpredictability of how sequence changes affect function. Here, we experimentally characterize the entire sequence phylogeny, comprising 1,158 extant and ancestral sequences, of the DNA-binding domain (DBD) of the LacI/GalR transcriptional repressor family. Our analysis revealed an extremely rugged landscape with rapid switching of specificity, even between adjacent nodes. Further, the ruggedness arises due to the necessity of the repressor to simultaneously evolve specificity for asymmetric operators and disfavors potentially adverse regulatory crosstalk. Our study provides fundamental insight into evolutionary, molecular, and biophysical rules of genetic regulation through the lens of fitness landscapes.
    MeSH term(s) Phylogeny
    Language English
    Publishing date 2024-03-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2854138-8
    ISSN 2405-4720 ; 2405-4712
    ISSN (online) 2405-4720
    ISSN 2405-4712
    DOI 10.1016/j.cels.2024.03.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article ; Online: Ancestral sequence reconstruction for protein engineers.

    Spence, Matthew A / Kaczmarski, Joe A / Saunders, Jake W / Jackson, Colin J

    Current opinion in structural biology

    2021  Volume 69, Page(s) 131–141

    Abstract: In addition to its value in the study of molecular evolution, ancestral sequence reconstruction (ASR) has emerged as a useful methodology for engineering proteins with enhanced properties. Proteins generated by ASR often exhibit unique or improved ... ...

    Abstract In addition to its value in the study of molecular evolution, ancestral sequence reconstruction (ASR) has emerged as a useful methodology for engineering proteins with enhanced properties. Proteins generated by ASR often exhibit unique or improved activity, stability, and/or promiscuity, all of which are properties that are valued by protein engineers. Comparison between extant proteins and evolutionary intermediates generated by ASR also allows protein engineers to identify substitutions that have contributed to functional innovation or diversification within protein families. As ASR becomes more widely adopted as a protein engineering approach, it is important to understand the applications, limitations, and recent developments of this technique. This review highlights recent exemplifications of ASR, as well as technical aspects of the reconstruction process that are relevant to protein engineering.
    MeSH term(s) Biological Evolution ; Evolution, Molecular ; Humans ; Phylogeny ; Protein Engineering ; Proteins/genetics
    Chemical Substances Proteins
    Language English
    Publishing date 2021-05-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1068353-7
    ISSN 1879-033X ; 0959-440X
    ISSN (online) 1879-033X
    ISSN 0959-440X
    DOI 10.1016/j.sbi.2021.04.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3206: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article ; Online: Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade.

    Burnim, Audrey A / Spence, Matthew A / Xu, Da / Jackson, Colin J / Ando, Nozomi

    eLife

    2022  Volume 11

    Abstract: Ribonucleotide reductases (RNRs) are used by all free-living organisms and many viruses to catalyze an essential step in the de novo biosynthesis of DNA precursors. RNRs are remarkably diverse by primary sequence and cofactor requirement, while sharing a ...

    Abstract Ribonucleotide reductases (RNRs) are used by all free-living organisms and many viruses to catalyze an essential step in the de novo biosynthesis of DNA precursors. RNRs are remarkably diverse by primary sequence and cofactor requirement, while sharing a conserved fold and radical-based mechanism for nucleotide reduction. Here, we structurally aligned the diverse RNR family by the conserved catalytic barrel to reconstruct the first large-scale phylogeny consisting of 6779 sequences that unites all extant classes of the RNR family and performed evo-velocity analysis to independently validate our evolutionary model. With a robust phylogeny in-hand, we uncovered a novel, phylogenetically distinct clade that is placed as ancestral to the classes I and II RNRs, which we have termed clade Ø. We employed small-angle X-ray scattering (SAXS), cryogenic-electron microscopy (cryo-EM), and AlphaFold2 to investigate a member of this clade from
    MeSH term(s) DNA ; Nucleotides ; Phylogeny ; Ribonucleotide Reductases/genetics ; Scattering, Small Angle ; X-Ray Diffraction
    Chemical Substances Nucleotides ; DNA (9007-49-2) ; Ribonucleotide Reductases (EC 1.17.4.-)
    Language English
    Publishing date 2022-09-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.79790
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top