NMRe: a web server for NMR protein structure refinement with high-quality structure validation scores

Ryu, Hyojung; Lim, Gyutae; Sung, Bong Hyun; Lee, Jinhyuk

doi:10.1093/bioinformatics/btv595

Cited by 6 publications

(5 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The secondary structure was predicted by CSI 3.0 webserver (50). Structure calculations were performed by dynamics simulated annealing method using Xplor-NIH software (51, 52) and refined via the NMRe web server (53). Structure refinement of the complex was performed using HADDOCK 2.2 server (54).…”

Section: Methodsmentioning

confidence: 99%

Tick saliva protein Evasin-3 modulates chemotaxis by disrupting CXCL8 interactions with glycosaminoglycans and CXCR2

Denisov

Ippel

Heinzmann

et al. 2019

Journal of Biological Chemistry

View full text Add to dashboard Cite

Chemokines are a group of chemotaxis proteins that regulate cell trafficking and play important roles in immune responses and inflammation. Ticks are blood-sucking parasites that secrete numerous immune-modulatory agents in their saliva to evade host immune responses. Evasin-3 is a small salivary protein that belongs to a class of chemokine-binding proteins isolated from the brown dog tick, Rhipicephalus sanguineus . Evasin-3 has been shown to have a high affinity for chemokines CXCL1 and CXCL8 and to diminish inflammation in mice. In the present study, solution NMR spectroscopy was used to investigate the structure of Evasin-3 and its CXCL8–Evasin-3 complex. Evasin-3 is found to disrupt the glycosaminoglycan-binding site of CXCL8 and inhibit the interaction of CXCL8 with CXCR2. Structural data were used to design two novel CXCL8-binding peptides. The linear tEv3 17–56 and cyclic tcEv3 16–56 dPG Evasin-3 variants were chemically synthesized by solid-phase peptide synthesis. The affinity of these newly synthesized variants to CXCL8 was measured by surface plasmon resonance biosensor analysis. The K d values of tEv3 17–56 and tcEv3 16–56 dPG were 27 and 13 n m , respectively. Both compounds effectively inhibited CXCL8-induced migration of polymorphonuclear neutrophils. The present results suggest utility of synthetic Evasin-3 variants as scaffolds for designing and fine-tuning new chemokine-binding agents that suppress immune responses and inflammation.

show abstract

Section: Methodsmentioning

confidence: 99%

Tick saliva protein Evasin-3 modulates chemotaxis by disrupting CXCL8 interactions with glycosaminoglycans and CXCR2

Denisov

Ippel

Heinzmann

et al. 2019

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Seven iterations of automatic NOESY cross peak and distance restraint assignments, along with stereospecific chemical shift assignments, were carried out. At each step, an ensemble of 100 structures was calculated, followed by a final ensemble calculation from which the 20 lowest energy structures were further refined using the original NOE distance restraints, NOE-like inter-proton distance restraints from the initially calculated structures, and a knowledge based Statistical Torsion Angle Potential (STAP) in NMRe (Ryu et al, 2016). Consensus secondary structure boundaries for the Rv1747 206-310 ensemble were determined using DSSP and the figures rendered using PyMol (Schrodinger, LLC).…”

Section: Synthetic Pthr-containing Rv1747 Peptidesmentioning

confidence: 99%

Biophysical Characterization of the Tandem FHA Domain Regulatory Module from the Mycobacterium tuberculosis ABC Transporter Rv1747

et al. 2018

View full text Add to dashboard Cite

The Mycobacterium tuberculosis ATP-binding cassette transporter Rv1747 is a putative exporter of cell wall biosynthesis intermediates. Rv1747 has a cytoplasmic regulatory module consisting of two pThr-interacting Forkhead-associated (FHA) domains connected by a conformationally disordered linker with two phospho-acceptor threonines (pThr). The structures of FHA-1 and FHA-2 were determined by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, respectively. Relative to the canonical 11-strand β-sandwich FHA domain fold of FHA-1, FHA-2 is circularly permuted and lacking one β-strand. Nevertheless, the two share a conserved pThr-binding cleft. FHA-2 is less stable and more dynamic than FHA-1, yet binds model pThr peptides with moderately higher affinity (∼50 μM versus 500 μM equilibrium dissociation constants). Based on NMR relaxation and chemical shift perturbation measurements, when joined within a polypeptide chain, either FHA domain can bind either linker pThr to form intra- and intermolecular complexes. We hypothesize that this enables tunable phosphorylation-dependent multimerization to regulate Rv1747 transporter activity.

show abstract

“…The latter were introduced only after initial calculations identified cysteine pairs within covalent bonding distances. CYANA-derived models were further refined with the CHARMM force field by being submitted to the NMRe server (). Structure validation was obtained through the wwPDB validation system ().…”

Section: Methodsmentioning

confidence: 99%

Ligand- and pH-Induced Structural Transition of Gypsy Moth Lymantria dispar Pheromone-Binding Protein 1 (LdisPBP1)

et al. 2020

View full text Add to dashboard Cite

Pheromone-binding proteins (PBPs) are small, water-soluble proteins found in the lymph of pheromone-sensing hairs. PBPs are essential in modulating pheromone partitioning in the lymph and at pheromone receptors of olfactory sensory neurons. The function of a PBP is associated with its ability to structurally convert between two conformations. Although mechanistic details remain unclear, it has been proposed that the structural transition between these forms is affected by two factors: pH and the presence or absence of ligand. To better understand the PBP conformational transition, the structure of the gypsy moth (Lymantria dispar) LdisPBP1 was elucidated at pH 4.5 and 35 °C using nuclear magnetic resonance spectroscopy. In addition, the effects of sample pH and binding of the species' pheromone, (+)-disparlure, (7R,8S)epoxy-2-methyloctadecane, and its enantiomer were monitored via 15 N HSQC spectroscopy. LdisPBP1 in acidic conditions has seven helices, with its C-terminal residues forming the seventh helix within the pheromone-binding pocket and its N-terminal residues disordered. Under conditions where this conformation is made favorable, free LdisPBP1 would have limited ligand binding capacity due to the seventh helix occupying the internal binding pocket. Our findings suggest that even in the presence of 4-fold ligand at acidic pH, LdisPBP1 is only ∼60% in its pheromone-bound form. Furthermore, evidence of a different LdisPBP1 form is seen at higher pH, with the transition pH between 5.6 and 6.0. This suggests that LdisPBP1 at neutral pH exists as a mixture of at least two conformations. These findings have implications concerning the PBP ligand binding and release mechanism.

show abstract

NMRe: a web server for NMR protein structure refinement with high-quality structure validation scores

Abstract: NMRe is available at http://psb.kobic.re.kr/nmre/.

Cited by 6 publications

References 11 publications

Tick saliva protein Evasin-3 modulates chemotaxis by disrupting CXCL8 interactions with glycosaminoglycans and CXCR2

Tick saliva protein Evasin-3 modulates chemotaxis by disrupting CXCL8 interactions with glycosaminoglycans and CXCR2

Biophysical Characterization of the Tandem FHA Domain Regulatory Module from the Mycobacterium tuberculosis ABC Transporter Rv1747

Ligand- and pH-Induced Structural Transition of Gypsy Moth Lymantria dispar Pheromone-Binding Protein 1 (LdisPBP1)

Contact Info

Product

Resources

About