IndraLab
Statements
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"Through FTMap (Kozakov et al., 2011) analysis of the MD simulation-derived structure of the OSM–OSMR complex, 10 potential druggable binding sites were detected from fragment-based searching of the global protein surface (Figure 3D), indicating that the conformation of the residues in the recognition interface is very flexible."
sparser
"Through FTMap (Kozakov et al., xref ) analysis of the MD simulation-derived structure of the OSM–OSMR complex, 10 potential druggable binding sites were detected from fragment-based searching of the global protein surface ( xref ), indicating that the conformation of the residues in the recognition interface is very flexible."
reach
"Starting from the crystal structure of OSM (Deller et al., 2000) and the model of the OSMR [a protein-binding region was built using the leukemia inhibitory factor receptor (LIFR) crystal structure (Huyton et al., 2007) as a template], the near-native conformation of the OSM–OSMR complex was obtained through protein–protein docking."
sparser
"Moreover, using the crystal structure of the LIF–LIFR complex (PDB code 2Q7N), CAS analysis was performed on residues (Pro51, Phe52, Pro53, Leu56, Pro106, Leu109, Phe156, Gln157, Ile234, Val258, Asn261, Ser262, Ile267, Ile310, and Leu313) corresponding to the residues (Arg39, Asp41, Val42, Leu45, Arg100, Leu103, Phe160, Gln161, Phe205, Asn208, Lys209, Tyr214, Asp262, and Leu265) located at same position in the OSM–OSMR interface."
sparser
"The predicted 3D structure of the OSM-OSMR complex and the identified "hot spots" constituting the core of the binding interface provide helpful information in understanding the OSM-OSMR interactions, and the detected sites serve as promising targets in designing small molecules to block the interactions."
sparser
"Moreover, the 18 residues (Cys179, Leu181, Phe205, Ile206, Asn208, Lys209, Gly210, Tyr214, Glu216, Gln219, Gly220, Asn221, Val222, Ser223, Asp262, Ala264, Leu265, and Trp267) characterized in the OSMR were informative in experimentally verifying these residues, which may play an important role in OSM and OSMR interaction (Huang et al., xref )."
reach
"The decomposed energy terms of the total binding free energy (G ) indicated that electrostatic interaction energy (E , −338.29 ± 44.73 kcal/mol), van der Waals interaction energy (E , −82.02 ± 7.17 kcal/mol), and non-polar solvent energy (G , −11.74 ± 1.08 kcal/mol) play important roles in the formation of the protein–protein complex, whereas polar solvent energies (G , 383.11 ± 43.06 kcal/mol) were unfavored for the interaction.In addition, per-residue energy decomposition analysis was performed to identify the important residues for the OSM–OSMR complex formation."
sparser
"To investigate the role of the OSMR SNP rs34675408 in HAEC susceptibility, we then evaluated the effect of OSM-OSMR activation in an HAEC patient homozygous for the T allele (LY3828) and in an HAEC patient homozygous for the HAEC associated G allele (LY4759) by pERK immunofluorescence analysis."
reach
"The predicted 3D structure of the OSM-OSMR complex and the identified "hot spots" constituting the core of the binding interface provide helpful information in understanding the OSM-OSMR interactions, and the detected sites serve as promising targets in designing small molecules to block the interactions."
reach
"It is of paramount importance to understand the details of the OSM and OSMR complex formation as well as the potential binding site between the protein–protein interface.In this work, molecular simulation approaches aimed at filling the aforementioned gap were performed to accelerate the discovery of small molecules targeting OSM–OSMR."
sparser
"Starting from the crystal structure of OSM (Deller et al., xref ) and the model of the OSMR [a protein-binding region was built using the leukemia inhibitory factor receptor (LIFR) crystal structure (Huyton et al., xref ) as a template], the near-native conformation of the OSM–OSMR complex was obtained through protein–protein docking."
sparser
"Our data suggest that OSM–OSMR interactions may also be responsible for inducing TGM2 in other cell types, such as breast cancer cells, in which OSM promotes cell motility and metastatic behaviour and TGM2 has been associated with migration, invasion and metastasis xref – xref ."
sparser
"Herein, to find the “hot spots” located at the OSM–OSMR interface, the computational alanine scanning (CAS) mutagenesis calculation was conducted on the residues with an absolute energy contribution of more than 1 kcal/mol identified by the per-residue energy decomposition analysis (Yang et al., xref ; Du et al., xref )."
reach
"Upon brain infiltration, macrophages release several cytokines and ligands such as oncostatin M, which binds to the oncostatin M receptor and leukemia inhibitory factor receptor that signals through the signal transducer and activator of transcript 3 pathway to induce the MES-like transcriptional program in glioma cells [22]."
| PMC
sparser
"Work in human fibroblast or epithelial cells show that OSM ligand binding to OSMR induces receptor degradation and then increases the level of receptor synthesis. xref In hepatocytes and hepatoma cells, OSM induces hypoxia-inducible factor 1α gene transcription via a Janus kinase/signal transducer. xref Considered in the context of the literature that indicates that OSM helps regulate erythropoiesis, the fact that we observed increased abundance of OSMR fragments in patients with poor EPO response might be expected."
reach
"OSM can form a
complex with either LIFR/gp130 or OSMR/gp130 , and therefore the effects of OSM and activation of
downstream signaling pathways such as STAT3, ERK, AKT, and Src signaling in breast
cancer cells may be mediated through either LIFR or OSMR, but previous studies have
not determined which receptor is responsible."
sparser
"The predicted 3D structure of the OSM–OSMR complex and the identified “hot spots” constituting the core of the binding interface provide helpful information in understanding the OSM–OSMR interactions, and the detected sites serve as promising targets in designing small molecules to block the interactions."
sparser
"Finally, the “hotspots” were mapped to the seven binding sites located at the OSM–OSMR interface detected using FTMap (Kozakov et al., xref ), and three of them were suggested as important target sites for future designs of small molecular modulators in the OSM–OSMR interaction."
reach
"Typically, OSM binding to the OSMR:gp130 complex causes the phosphorylation and activation of both STAT1 and STAT3 via JAK1/2 (23, 24) which in turns leads the transcription of a large range of genes that include suppressor of cytokine signaling (SOCS)-3. A negative feed-back loop is triggered by SOCS3, which binds to both gp130 and activated JAKs, suppressing this signaling cascade and STAT1 and STAT3 activation (25, 26)."
reach
"The predicted 3D structure of the OSM and OSMR complex and the identified " hot spots " constituting the core of the binding interface provide helpful information in understanding the OSM-OSMR interactions, and the detected sites serve as promising targets in designing small molecules to block the interactions."