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Papers by Eiso AB

Research paper thumbnail of Automatic Assignment of Methyl-NMR Spectra of Supramolecular Machines Using Graph Theory

Journal of the American Chemical Society, Jul 10, 2017

Research paper thumbnail of Interrogating the Essential Bacterial Cell Division Protein FtsQ with Fragments Using Target Immobilized NMR Screening (TINS)

International Journal of Molecular Sciences, Jul 27, 2019

Research paper thumbnail of The high-resolution NMR structure of the R21A Spc-SH3:P41 complex: Understanding the determinants of binding affinity by comparison with Abl-SH3

BMC Structural Biology, Apr 2, 2007

Research paper thumbnail of Structural studies on IIBChb

We willen graag uitvinden hoe de eiwitten van het PTS op moleculair niveau werken, bijvoorbeeld w... more We willen graag uitvinden hoe de eiwitten van het PTS op moleculair niveau werken, bijvoorbeeld wat de moleculaire verklaring is voor deze communicatieprocessen, of hoe de overdracht van de fosforylgroep tussen de eiwitten en tussen eiwit en suiker plaatsvindt. Hiervoor is het nodig om de structuren van de eiwitten in kwestie te bepalen. Dit betekent voor IIBchb bovendien dat we zouden willen weten hoe de fosforylering van IIBchb door IIAchb plaatsvindt, en hoe IIBchb vervolgens aan IICchb bindt en de suiker getransporteerd en gefosforyleerd wordt. Zie: Samenvatting

Research paper thumbnail of NMR in target driven drug discovery: why not?

Journal of Biomolecular NMR, 2020

No matter the source of compounds, drug discovery campaigns focused directly on the target are en... more No matter the source of compounds, drug discovery campaigns focused directly on the target are entirely dependent on a consistent stream of reliable data that reports on how a putative ligand interacts with the protein of interest. The data will derive from many sources including enzyme assays and many types of biophysical binding assays such as TR-FRET, SPR, thermophoresis and many others. Each method has its strengths and weaknesses, but none is as information rich and broadly applicable as NMR. Here we provide a number of examples of the utility of NMR for enabling and providing ongoing support for the early pre-clinical phase of small molecule drug discovery efforts. The examples have been selected for their usefulness in a commercial setting, with full understanding of the need for speed, cost-effectiveness and ease of implementation.

Research paper thumbnail of Fragment-derived modulators of an industrial β-glucosidase

Biochemical Journal, 2020

A fragment screen of a library of 560 commercially available fragments using a kinetic assay iden... more A fragment screen of a library of 560 commercially available fragments using a kinetic assay identified a small molecule that increased the activity of the fungal glycoside hydrolase TrBgl2. An analogue by catalogue approach and detailed kinetic analysis identified improved compounds that behaved as nonessential activators with up to a 2-fold increase in maximum activation. The compounds did not activate the related bacterial glycoside hydrolase CcBglA demonstrating specificity. Interestingly, an analogue of the initial fragment inhibits both TrBgl2 and CcBglA, apparently through a mixed-model mechanism. Although it was not possible to determine crystal structures of activator binding to 55 kDa TrBgl2, solution NMR experiments demonstrated a specific binding site for the activator. A partial assignment of the NMR spectrum gave the identity of the amino acids at this site, allowing a model for TrBgl2 activation to be built. The activator binds at the entrance of the substrate-binding...

Research paper thumbnail of Correction to: 1H, 13C, 15N backbone and IVL methyl group resonance assignment of the fungal β-glucosidase from Trichoderma reesei

Biomolecular NMR Assignments, 2020

In the original publication of the article, the name of one of the authors is incorrect. The auth... more In the original publication of the article, the name of one of the authors is incorrect. The author's name is Eiso AB, but was modified to A. B. Eiso. The correct name is given in this Correction.

Research paper thumbnail of Automatic Assignment of Methyl-NMR Spectra of Supramolecular Machines Using Graph Theory

Journal of the American Chemical Society, 2017

Research paper thumbnail of Solution Structure of E. coli IIBcellobiose of the PEP-dependent PTS

Progress in Biophysics and Molecular Biology

Research paper thumbnail of DWNN, a novel ubiquitin-like domain, implicates RBBP6 in mRNA processing and ubiquitin-like pathways

Research paper thumbnail of Structure and DNA Binding of the Human Rtf1 Plus3 Domain

Research paper thumbnail of The NMR side‐chain assignments and solution structure of enzyme HBcellobiose of the phosphoenolpyruvate‐dependent phosphotransferase system of Escherichia coli

Protein Science, 2008

The assignment of the side‐chain NMR resonances and the determination of the three‐dimensional so... more The assignment of the side‐chain NMR resonances and the determination of the three‐dimensional solution structure of the C10S mutant of enzyme IIBcellobiose (IIBcel) of the phosphoenolpyruvate‐dependent phosphotransferase system of Escherichia coli are presented. The side‐chain resonances were assigned nearly completely using a variety of mostly heteronuclear NMR experiments, including HCCH‐TOCSY, HCCH‐COSY, and COCCH‐TOCSY experiments as well as CBCACOHA, CBCA(CO)NH, and HBHA(CBCA)(CO)NH experiments.In order to obtain the three‐dimensional structure, NOE data were collected from l5N‐NOESY‐HSQC, 13C‐HSQC‐NOESY, and 2D NOE experiments. The distance restraints derived from these NOE data were used in distance geometry calculations followed by molecular dynamics and simulated annealing protocols. In an iterative procedure, additional NOE assignments were derived from the calculated structures and new structures were calculated. The final set of structures, calculated with approximately...

Research paper thumbnail of X-ray structure of phospholipase A2 complexed with a substrate-derived inhibitor

Research paper thumbnail of NMR structure of cysteinyl-phosphorylated enzyme IIB of the N,N′-diacetylchitobiose-specific phosphoenolpyruvate-dependent phosphotransferase system of Escherichia coli

Journal of Molecular Biology, 2001

Research paper thumbnail of Rapid Protein–Ligand Costructures from Sparse NOE Data

Journal of Medicinal Chemistry, 2012

An efficient way to rapidly generate protein-ligand costructures based on solution-NMR using spar... more An efficient way to rapidly generate protein-ligand costructures based on solution-NMR using sparse NOE data combined with selective isotope labeling is presented. A docked model of the 27 kDa N-terminal ATPase domain of Hsp90 bound to a small molecule ligand was generated using only 21 intermolecular NOEs, which uniquely defined both the binding site and the orientation of the ligand. The approach can prove valuable for the early stages of fragment-based drug discovery.

Research paper thumbnail of Correlation of the15N(i+ 1),13Cα(i), and1Hα(i) Backbone Resonances in13C/15N-Labeled Proteins by the (CO)N(CO)CAH Experiment

Journal of Magnetic Resonance, 1997

Research paper thumbnail of Target Immobilization as a Strategy for NMR-Based Fragment Screening: Comparison of TINS, STD, and SPR for Fragment Hit Identification

SLAS Discovery, 2010

Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to h... more Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing small-molecule inhibitors of pharmaceutical targets. Because a fragment campaign can only be as successful as the hit matter found, it is critical that the first stage of the process be optimized. Here the authors compare the 3 most commonly used methods for hit discovery in FBDD: high concentration screening (HCS), solution ligand-observed nuclear magnetic resonance (NMR), and surface plasmon resonance (SPR). They selected the commonly used saturation transfer difference (STD) NMR spectroscopy and the proprietary target immobilized NMR screening (TINS) as representative of the array of possible NMR methods. Using a target typical of FBDD campaigns, the authors find that HCS and TINS are the most sensitive to weak interactions. They also find a good correlation between TINS and STD for tighter binding ligands, but the ability of STD to detect ...

Research paper thumbnail of Solution Structure of RING Finger-like Domain of Retinoblastoma-binding Protein-6 (RBBP6) Suggests It Functions as a U-box

Journal of Biological Chemistry, 2012

Research paper thumbnail of Structure of the DNA-bound BRCA1 C-terminal Region from Human Replication Factor C p140 and Model of the Protein-DNA Complex

Journal of Biological Chemistry, 2010

Research paper thumbnail of The Structure of Bypass of Forespore C, an Intercompartmental Signaling Factor during Sporulation in Bacillus

Journal of Biological Chemistry, 2005

Research paper thumbnail of Automatic Assignment of Methyl-NMR Spectra of Supramolecular Machines Using Graph Theory

Journal of the American Chemical Society, Jul 10, 2017

Research paper thumbnail of Interrogating the Essential Bacterial Cell Division Protein FtsQ with Fragments Using Target Immobilized NMR Screening (TINS)

International Journal of Molecular Sciences, Jul 27, 2019

Research paper thumbnail of The high-resolution NMR structure of the R21A Spc-SH3:P41 complex: Understanding the determinants of binding affinity by comparison with Abl-SH3

BMC Structural Biology, Apr 2, 2007

Research paper thumbnail of Structural studies on IIBChb

We willen graag uitvinden hoe de eiwitten van het PTS op moleculair niveau werken, bijvoorbeeld w... more We willen graag uitvinden hoe de eiwitten van het PTS op moleculair niveau werken, bijvoorbeeld wat de moleculaire verklaring is voor deze communicatieprocessen, of hoe de overdracht van de fosforylgroep tussen de eiwitten en tussen eiwit en suiker plaatsvindt. Hiervoor is het nodig om de structuren van de eiwitten in kwestie te bepalen. Dit betekent voor IIBchb bovendien dat we zouden willen weten hoe de fosforylering van IIBchb door IIAchb plaatsvindt, en hoe IIBchb vervolgens aan IICchb bindt en de suiker getransporteerd en gefosforyleerd wordt. Zie: Samenvatting

Research paper thumbnail of NMR in target driven drug discovery: why not?

Journal of Biomolecular NMR, 2020

No matter the source of compounds, drug discovery campaigns focused directly on the target are en... more No matter the source of compounds, drug discovery campaigns focused directly on the target are entirely dependent on a consistent stream of reliable data that reports on how a putative ligand interacts with the protein of interest. The data will derive from many sources including enzyme assays and many types of biophysical binding assays such as TR-FRET, SPR, thermophoresis and many others. Each method has its strengths and weaknesses, but none is as information rich and broadly applicable as NMR. Here we provide a number of examples of the utility of NMR for enabling and providing ongoing support for the early pre-clinical phase of small molecule drug discovery efforts. The examples have been selected for their usefulness in a commercial setting, with full understanding of the need for speed, cost-effectiveness and ease of implementation.

Research paper thumbnail of Fragment-derived modulators of an industrial β-glucosidase

Biochemical Journal, 2020

A fragment screen of a library of 560 commercially available fragments using a kinetic assay iden... more A fragment screen of a library of 560 commercially available fragments using a kinetic assay identified a small molecule that increased the activity of the fungal glycoside hydrolase TrBgl2. An analogue by catalogue approach and detailed kinetic analysis identified improved compounds that behaved as nonessential activators with up to a 2-fold increase in maximum activation. The compounds did not activate the related bacterial glycoside hydrolase CcBglA demonstrating specificity. Interestingly, an analogue of the initial fragment inhibits both TrBgl2 and CcBglA, apparently through a mixed-model mechanism. Although it was not possible to determine crystal structures of activator binding to 55 kDa TrBgl2, solution NMR experiments demonstrated a specific binding site for the activator. A partial assignment of the NMR spectrum gave the identity of the amino acids at this site, allowing a model for TrBgl2 activation to be built. The activator binds at the entrance of the substrate-binding...

Research paper thumbnail of Correction to: 1H, 13C, 15N backbone and IVL methyl group resonance assignment of the fungal β-glucosidase from Trichoderma reesei

Biomolecular NMR Assignments, 2020

In the original publication of the article, the name of one of the authors is incorrect. The auth... more In the original publication of the article, the name of one of the authors is incorrect. The author's name is Eiso AB, but was modified to A. B. Eiso. The correct name is given in this Correction.

Research paper thumbnail of Automatic Assignment of Methyl-NMR Spectra of Supramolecular Machines Using Graph Theory

Journal of the American Chemical Society, 2017

Research paper thumbnail of Solution Structure of E. coli IIBcellobiose of the PEP-dependent PTS

Progress in Biophysics and Molecular Biology

Research paper thumbnail of DWNN, a novel ubiquitin-like domain, implicates RBBP6 in mRNA processing and ubiquitin-like pathways

Research paper thumbnail of Structure and DNA Binding of the Human Rtf1 Plus3 Domain

Research paper thumbnail of The NMR side‐chain assignments and solution structure of enzyme HBcellobiose of the phosphoenolpyruvate‐dependent phosphotransferase system of Escherichia coli

Protein Science, 2008

The assignment of the side‐chain NMR resonances and the determination of the three‐dimensional so... more The assignment of the side‐chain NMR resonances and the determination of the three‐dimensional solution structure of the C10S mutant of enzyme IIBcellobiose (IIBcel) of the phosphoenolpyruvate‐dependent phosphotransferase system of Escherichia coli are presented. The side‐chain resonances were assigned nearly completely using a variety of mostly heteronuclear NMR experiments, including HCCH‐TOCSY, HCCH‐COSY, and COCCH‐TOCSY experiments as well as CBCACOHA, CBCA(CO)NH, and HBHA(CBCA)(CO)NH experiments.In order to obtain the three‐dimensional structure, NOE data were collected from l5N‐NOESY‐HSQC, 13C‐HSQC‐NOESY, and 2D NOE experiments. The distance restraints derived from these NOE data were used in distance geometry calculations followed by molecular dynamics and simulated annealing protocols. In an iterative procedure, additional NOE assignments were derived from the calculated structures and new structures were calculated. The final set of structures, calculated with approximately...

Research paper thumbnail of X-ray structure of phospholipase A2 complexed with a substrate-derived inhibitor

Research paper thumbnail of NMR structure of cysteinyl-phosphorylated enzyme IIB of the N,N′-diacetylchitobiose-specific phosphoenolpyruvate-dependent phosphotransferase system of Escherichia coli

Journal of Molecular Biology, 2001

Research paper thumbnail of Rapid Protein–Ligand Costructures from Sparse NOE Data

Journal of Medicinal Chemistry, 2012

An efficient way to rapidly generate protein-ligand costructures based on solution-NMR using spar... more An efficient way to rapidly generate protein-ligand costructures based on solution-NMR using sparse NOE data combined with selective isotope labeling is presented. A docked model of the 27 kDa N-terminal ATPase domain of Hsp90 bound to a small molecule ligand was generated using only 21 intermolecular NOEs, which uniquely defined both the binding site and the orientation of the ligand. The approach can prove valuable for the early stages of fragment-based drug discovery.

Research paper thumbnail of Correlation of the15N(i+ 1),13Cα(i), and1Hα(i) Backbone Resonances in13C/15N-Labeled Proteins by the (CO)N(CO)CAH Experiment

Journal of Magnetic Resonance, 1997

Research paper thumbnail of Target Immobilization as a Strategy for NMR-Based Fragment Screening: Comparison of TINS, STD, and SPR for Fragment Hit Identification

SLAS Discovery, 2010

Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to h... more Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing small-molecule inhibitors of pharmaceutical targets. Because a fragment campaign can only be as successful as the hit matter found, it is critical that the first stage of the process be optimized. Here the authors compare the 3 most commonly used methods for hit discovery in FBDD: high concentration screening (HCS), solution ligand-observed nuclear magnetic resonance (NMR), and surface plasmon resonance (SPR). They selected the commonly used saturation transfer difference (STD) NMR spectroscopy and the proprietary target immobilized NMR screening (TINS) as representative of the array of possible NMR methods. Using a target typical of FBDD campaigns, the authors find that HCS and TINS are the most sensitive to weak interactions. They also find a good correlation between TINS and STD for tighter binding ligands, but the ability of STD to detect ...

Research paper thumbnail of Solution Structure of RING Finger-like Domain of Retinoblastoma-binding Protein-6 (RBBP6) Suggests It Functions as a U-box

Journal of Biological Chemistry, 2012

Research paper thumbnail of Structure of the DNA-bound BRCA1 C-terminal Region from Human Replication Factor C p140 and Model of the Protein-DNA Complex

Journal of Biological Chemistry, 2010

Research paper thumbnail of The Structure of Bypass of Forespore C, an Intercompartmental Signaling Factor during Sporulation in Bacillus

Journal of Biological Chemistry, 2005