Search results for "protein conformation"
showing 10 items of 515 documents
Mona/Gads SH3C binding to hematopoietic progenitor kinase 1 (HPK1) combines an atypical SH3 binding motif, R/KXXK, with a classical PXXP motif embedd…
2004
Hematopoietic progenitor kinase 1 (HPK1) is implicated in signaling downstream of the T cell receptor. Its non-catalytic, C-terminal half contains several prolinerich motifs, which have been shown to interact with different SH3 domain-containing adaptor proteins in vitro. One of these, Mona/Gads, was also shown to bind HPK1 in mouse T cells in vivo. The region of HPK1 that binds to the Mona/Gads C-terminal SH3 domain has been mapped and shows only very limited similarity to a recently identified high affinity binding motif in SLP-76, another T-cell adaptor. Using isothermal titration calorimetry and x-ray crystallography, the binding of the HPK1 motif to Mona/Gads SH3C has now been characte…
Quenching of fluorescein-conjugated lipids by antibodies. Quantitative recognition and binding of lipid-bound haptens in biomembrane models, formatio…
1992
Three model biomembrane systems, monolayers, micelles, and vesicles, have been used to study the influence of chemical and physical variables of hapten presentation at membrane interfaces on antibody binding. Hapten recognition and binding were monitored for the anti-fluorescein monoclonal antibody 4–4-20 generated against the hapten, fluorescein, in these membrane models as a function of fluorescein-conjugated lipid architecture. Specific recognition and binding in this system are conveniently monitored by quenching of fluorescein emission upon penetration of fluorescein into the antibody's active site. Lipid structure was shown to play a large role in affecting antibody quenching. Interes…
Modeling of the role of conformational dynamics in kinetics of the antigen-antibody interaction in heterogeneous phase.
2012
[EN] A novel approach that may potentially be used to study biomolecular interactions including the simultaneous determination of structural and kinetic binding parameters is described in this Article for the first time. It allows a rigid distinction between the possible reaction mechanisms of biomolecular recognition, induced fit and conformational selection. The relative importance of the two pathways is determined not by comparing rate constants but the structural aspects of the interaction instead. So the exact location of antigen molecules with respect to the capture antibody is depicted experimentally, avoiding the use of X-ray crystallography. The proposed pattern is applied to study…
The Structure of Rauvolfia serpentina Strictosidine Synthase Is a Novel Six-Bladed β-Propeller Fold in Plant Proteins
2006
Abstract The enzyme strictosidine synthase (STR1) from the Indian medicinal plant Rauvolfia serpentina is of primary importance for the biosynthetic pathway of the indole alkaloid ajmaline. Moreover, STR1 initiates all biosynthetic pathways leading to the entire monoterpenoid indole alkaloid family representing an enormous structural variety of ∼2000 compounds in higher plants. The crystal structures of STR1 in complex with its natural substrates tryptamine and secologanin provide structural understanding of the observed substrate preference and identify residues lining the active site surface that contact the substrates. STR1 catalyzes a Pictet-Spengler–type reaction and represents a novel…
Molecular and topological membrane folding determinants of transient receptor potential vanilloid 2 channel.
2015
Transient Receptor Potential (TRP) channels are related to adaptation to the environment and somatosensation. The transient receptor potential vanilloid (TRPV) subfamily includes six closely evolutionary related ion channels sharing the same domain organization and tetrameric arrangement in the membrane. In this study we have characterized biochemically TRPV2 channel membrane protein folding and transmembrane (TM) architecture. Deleting the first N-terminal 74 residues preceding the ankyrin repeat domain (ARD) show a key role for this region in targeting the protein to the membrane. We have demonstrated the co-translational insertion of the membrane-embedded region of the TRPV2 and its disp…
A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses.
2002
Virus like particles (VLPs) are known to induce potent B cell responses in the absence of adjuvants. Moreover, epitope-specific antibody responses may be induced by VLPs that contain peptides inserted in their immunodominant regions. However, due to steric problems, the size of the peptides capable of being incorporated into VLPs while still permitting capsid assembly, is rather limited. While peptides genetically fused to either the N- or C-terminus of VLPs present fewer assembly problems, the immune responses obtained against such epitopes are often limited, most likely because the epitopes are not optimally exposed. In addition, such particles may be less stable in vivo. Here, we show th…
Insights into virus evolution and membrane biogenesis from the structure of the marine lipid-containing bacteriophage PM2.
2008
Recent, primarily structural observations indicate that related viruses, harboring no sequence similarity, infect hosts of different domains of life. One such clade of viruses, defined by common capsid architecture and coat protein fold, is the so-called PRD1-adenovirus lineage. Here we report the structure of the marine lipid-containing bacteriophage PM2 determined by crystallographic analyses of the entire approximately 45 MDa virion and of the outer coat proteins P1 and P2, revealing PM2 to be a primeval member of the PRD1-adenovirus lineage with an icosahedral shell and canonical double beta barrel major coat protein. The view of the lipid bilayer, richly decorated with membrane protein…
Efficient virtual screening using multiple protein conformations described as negative images of the ligand-binding site.
2010
The protein structure-based virtual screening is typically accomplished using a molecular docking procedure. However, docking is a fairly slow process that is limited by the available scoring functions that cannot reliably distinguish between active and inactive ligands. In contrast, the ligand-based screening methods that are based on shape similarity identify the active ligands with high accuracy. Here, we show that the usage of negative images of the ligand-binding site, together with shape comparison tools, which are typically used in ligand-based virtual screening, improve the discrimination of active molecules from inactives. In contrast to ligand-based shape comparison, the negative …
Protein knot server: detection of knots in protein structures
2007
KNOTS (http://knots.mit.edu) is a web server that detects knots in protein structures. Several protein structures have been reported to contain intricate knots. The physiological role of knots and their effect on folding and evolution is an area of active research. The user submits a PDB id or uploads a 3D protein structure in PDB or mmCIF format. The current implementation of the server uses the Alexander polynomial to detect knots. The results of the analysis that are presented to the user are the location of the knot in the structure, the type of the knot and an interactive visualization of the knot. The results can also be downloaded and viewed offline. The server also maintains a regul…
A Computational Study of the Protein-Ligand Interactions in CDK2 Inhibitors: Using Quantum Mechanics/Molecular Mechanics Interaction Energy as a Pred…
2006
ABSTRACT: We report a combined quantum mechanics/molecular mechanics (QM/MM) study to determine the protein-ligand interaction energy between CDK2 (cyclin-dependent kinase 2) and five inhibitors with the N2 -substituted 6-cyclohexylmethoxypurine scaffold. The computational results in this work show that the QM/MM interaction energy is strongly correlated to the biological activity and can be used as a predictor, at least within a family of substrates. A detailed analysis of the protein-ligand structures obtained from molecular dynamics simulations shows specific interactions within the active site that, in some cases, have not been reported before to our knowledge. The computed interaction …