scholarly journals Solution structure of a small protein containing a fluorinated side chain in the core

2006 ◽  
Vol 16 (1) ◽  
pp. 14-19 ◽  
Author(s):  
G. Cornilescu ◽  
E. B. Hadley ◽  
M. G. Woll ◽  
J. L. Markley ◽  
S. H. Gellman ◽  
...  
Keyword(s):  
Solution Structure ◽  
Side Chain ◽  
Small Protein ◽  
The Core

scholarly journals The Solution Structure of the Human ETS1-DNA Complex Reveals a Novel Mode of Binding and True Side Chain Intercalation

Cell ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 358 ◽  
Author(s):  
Milton H Werner ◽  
G.Marius Clore ◽  
Constance L Fisher ◽  
Robert J Fisher ◽  
Loc Trinh ◽  
...  
Keyword(s):  
Solution Structure ◽  
Side Chain ◽  
Dna Complex

scholarly journals Structure of Nanobody Nb23

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3567
Author(s):  
Mathias Percipalle ◽  
Yamanappa Hunashal ◽  
Jan Steyaert ◽  
Federico Fogolari ◽  
Gennaro Esposito
Keyword(s):  
Nmr Spectroscopy ◽  
Chemical Shift ◽  
Solution Structure ◽  
Chemical Shifts ◽  
Molecular Size ◽  
Side Chain ◽  
3D Nmr ◽  
Target Antigen ◽  
Internuclear Distances ◽  
2D And 3D

Background: Nanobodies, or VHHs, are derived from heavy chain-only antibodies (hcAbs) found in camelids. They overcome some of the inherent limitations of monoclonal antibodies (mAbs) and derivatives thereof, due to their smaller molecular size and higher stability, and thus present an alternative to mAbs for therapeutic use. Two nanobodies, Nb23 and Nb24, have been shown to similarly inhibit the self-aggregation of very amyloidogenic variants of β2-microglobulin. Here, the structure of Nb23 was modeled with the Chemical-Shift (CS)-Rosetta server using chemical shift assignments from nuclear magnetic resonance (NMR) spectroscopy experiments, and used as prior knowledge in PONDEROSA restrained modeling based on experimentally assessed internuclear distances. Further validation was comparatively obtained with the results of molecular dynamics trajectories calculated from the resulting best energy-minimized Nb23 conformers. Methods: 2D and 3D NMR spectroscopy experiments were carried out to determine the assignment of the backbone and side chain hydrogen, nitrogen and carbon resonances to extract chemical shifts and interproton separations for restrained modeling. Results: The solution structure of isolated Nb23 nanobody was determined. Conclusions: The structural analysis indicated that isolated Nb23 has a dynamic CDR3 loop distributed over different orientations with respect to Nb24, which could determine differences in target antigen affinity or complex lability.

scholarly journals Interaction of human CYP17 (P-45017α, 17α-hydroxylase-17,20-lyase) with cytochrome b5: importance of the orientation of the hydrophobic domain of cytochrome b5

1997 ◽  
Vol 321 (3) ◽  
pp. 857-864 ◽  
Author(s):  
Peter LEE-ROBICHAUD ◽  
Mustak A. KADERBHAI ◽  
Naheed KADERBHAI ◽  
J. Neville WRIGHT ◽  
Muhammad AKHTAR
Keyword(s):  
Signal Sequence ◽  
Cytochrome B5 ◽  
Amino Acid Sequences ◽  
Side Chain ◽  
Hydrophobic Domain ◽  
Side Chain Cleavage ◽  
The Core ◽  
Cleavage Activity ◽  
P450 Reductase ◽  
Chain Cleavage

Human CYP17 (P-45017α, 17α-hydroxylase-17,20-lyase)-catalysed side-chain cleavage of 17α-hydroxyprogestogens into androgens is greatly dependent on the presence of cytochrome b5. The native form of cytochrome b5 is composed of a globular core, residues 1Ő98, followed by a membrane insertable C-terminal tail, residues 99Ő133. In the present study the abilities of five different forms of cytochrome b5 to support the side-chain cleavage activity of CYP17 were compared. The five derivatives were: the native pig cytochrome b5 (native pig), its genetically engineered rat counterpart (coreŐtail), the soluble core form of the latter (core), the core with the secretory signal sequence of alkaline phosphatase appended to its N-terminal (signalŐcore) and the latter containing the C-terminal tail of the native rat protein (signalŐcoreŐtail). When examined by Edman degradation and MS, the engineered proteins were shown to have the expected N-terminal amino acid sequences and molecular masses. The native pig was found to be acetylated at the N-terminal. The native pig and coreŐtail enzymes were equally efficient at enhancing the side-chain cleavage activity of human CYP17 and the signalŐcoreŐtail was 55% as efficient. The core and signalŐcore constructs were completely inactive in the aforementioned reaction. All the five derivatives were reduced to varying degrees by NADPH:cytochrome P-450 (NADPH-P450) reductase and the relative efficiencies of this reduction were reminiscent of the behaviour of these derivatives in supporting the side-chain cleavage reaction. In the side-chain cleavage assay, however, NADPH-P450 reductase was used in large excess so that the reduction of cytochrome b5 derivatives was not rate-limiting. The results highlight that productive interaction between cytochrome b5 and CYP17 is governed not only by the presence of a membrane insertable hydrophobic region on the cytochrome b5 but also by its defined spatial orientation at the C-terminal.

Synthesis and Solution Structure of 1H-Benzo-1,5-diazepine Derivatives with a Perfluoroalkyl Side Chain

2016 ◽  
Vol 99 (5) ◽  
pp. 361-372 ◽  
Author(s):  
Willi Desens ◽  
Marleen Winterberg ◽  
Dirk Michalik ◽  
Peter Langer
Keyword(s):  
Solution Structure ◽  
Side Chain

The Single Disulfide-Directed β-Hairpin Fold: Role of Disulfide Bond in Folding and Effect of an Additional Disulfide Bond on Stability

2020 ◽  
Vol 73 (4) ◽  
pp. 312
Author(s):  
Balasubramanyam Chittoor ◽  
Bankala Krishnarjuna ◽  
Rodrigo A. V. Morales ◽  
Raymond S. Norton
Keyword(s):  
Disulfide Bond ◽  
Disulfide Bonds ◽  
Solution Structure ◽  
Conformational Stability ◽  
Disulfide Bridge ◽  
Solution Nmr ◽  
Peptide Epitope ◽  
The Core ◽  
Native Fold

Disulfide bonds play a key role in the oxidative folding, conformational stability, and functional activity of many peptides. A few disulfide-rich peptides with privileged architecture such as the inhibitor cystine knot motif have garnered attention as templates in drug design. The single disulfide-directed β-hairpin (SDH), a novel fold identified more recently in contryphan-Vc1, has been shown to possess remarkable thermal, conformational, and chemical stability and can accept a short bioactive epitope without compromising the core structure of the peptide. In this study, we demonstrated that the single disulfide bond is critical in maintaining the native fold by replacing both cysteine residues with serine. We also designed an analogue with an additional, non-native disulfide bridge by replacing Gln1 and Tyr9 with Cys. Contryphan-Vc11–22[Q1C, Y9C] was synthesised utilising orthogonal cysteine protection and its solution structure determined using solution NMR spectroscopy. This analogue maintained the overall fold of native contryphan-Vc1. Previous studies had shown that the β-hairpin core of contryphan-Vc1 was resistant to proteolysis by trypsin and α-chymotrypsin but susceptible to cleavage by pepsin. Contryphan-Vc11–22[Q1C, Y9C] proved to be completely resistant to pepsin, thus confirming our design strategy. These results highlight the role of the disulfide bond in maintaining the SDH fold and provide a basis for the design of more stable analogues for peptide epitope grafting.

scholarly journals Proteoglycans of hyaline cartilage: Electron-microscopic studies on isolated molecules

1975 ◽  
Vol 151 (1) ◽  
pp. 157-166 ◽  
Author(s):  
J Thyberg ◽  
S Lohmander ◽  
D Heinegård
Keyword(s):  
Hyaline Cartilage ◽  
Chondroitin Sulphate ◽  
Costal Cartilage ◽  
Side Chain ◽  
Gel Chromatography ◽  
Electron Microscopic ◽  
The Core ◽  
Central Filament ◽  
Microscopic Studies ◽  
Chondroitin Sulphate Chain

Proteoglycan monomers from guinea-pig costal cartilage, bovine nasal and bovine tracheal cartilage were observed in the electron microscope after being spread in a monomolecular layer with cytochrome c. The proteoglycan molecule appeared as an extended central core filament to which side-chain filaments were attached at various intervals. The molecules from the three sources displayed great ultrastructural similarities. On average, the core filament was about 290 nm long, there were about 25 side-chain filaments per core filament, the side-chain filaments were about 45 nm long, and the distance between the attachment points of the side-chain filaments to the core filament was about 11 nm. With regard to the overall size of the molecules, no evidence of distinct subpopulations was obtained. Good correlation was found between ultrastructural data for the proteoglycan molecules and chemical data obtained by enzyme digestions and gel chromatography. Together these data strongly support the interpretation of the electron-microscopic pictures as indicating a central filament corresponding to the protein core and side-chain filaments corresponding to the chondroitin sulphate chain clusters of the proteoglycan monomers.

scholarly journals Backbone and side-chain ordering in a small protein

2008 ◽  
Vol 128 (2) ◽  
pp. 025105 ◽  
Author(s):  
Yanjie Wei ◽  
Walter Nadler ◽  
Ulrich H. E. Hansmann
Keyword(s):  
Side Chain ◽  
Small Protein ◽  
Chain Ordering

scholarly journals pH-dependent polymorphism of the structure of SARS-CoV-2 nsp7

2021 ◽  
Author(s):  
Yeongjoon Lee ◽  
Marco Tonelli ◽  
Mehdi Rahimi ◽  
Thomas K. Anderson ◽  
Robert N. Kirchdoerfer ◽  
...  
Keyword(s):  
Solution Structure ◽  
Structural Variation ◽  
Nonstructural Protein ◽  
Dynamic Properties ◽  
Intramolecular Interactions ◽  
Protonation State ◽  
Helical Bundle ◽  
The Core ◽  
Neutral Ph ◽  
Loop Regions

AbstractThe solution structure of SARS-CoV-2 nonstructural protein 7 (nsp7) at pH 7.0 has been determined by NMR spectroscopy. nsp7 is conserved in the coronavirinae subfamily and is an essential co-factor of the viral RNA-dependent RNA polymerase for active and processive replication. Similar to the previously deposited structures of SARS-CoV-1 nsp7 at acidic and basic conditions, SARS-CoV-2 nsp7 has a helical bundle folding at neutral pH. Remarkably, the α4 helix shows gradual dislocation from the core α2-α3 structure as pH increases from 6.5 to 7.5. The protonation state of residue H36 contributes to the change of nsp7’s intramolecular interactions, and thus, to the structural variation near-neutral pH. Spin-relaxation results revealed that all three loop regions in nsp7 possess dynamic properties associated with this structural variation.

scholarly journals Crystal structures of taxane-tubulin complexes: Implications for the mechanism of microtubule stabilization by Taxol

2021 ◽  
Author(s):  
Andrea Enrico Prota ◽  
Daniel Lucena-Agell ◽  
Yuntao Ma ◽  
Juan Estevez-Gallego ◽  
Carlos Roca ◽  
...  
Keyword(s):  
Conformational Transition ◽  
Core Structure ◽  
Side Chain ◽  
Binding Modes ◽  
Chemotherapeutic Drug ◽  
First Line ◽  
Baccatin Iii ◽  
Microtubule Stabilization ◽  
The Core ◽  
Microtubule Formation

Paclitaxel (Taxol) is a first-line chemotherapeutic drug that promotes the curved to straight conformational transition of tubulin, an activation step that is necessary for microtubule formation. Crystallization of Taxol bound to tubulin has been long elusive. We found that baccatin III, the core structure of paclitaxel which lacks the C13 side chain, readily co-crystallizes with curved tubulin. Tailor-made taxanes with alternative side chains also co-crystallized, allowing us to investigate their binding modes. Interestingly, these Taxol derived compounds lost their microtubule stabilizing activity and cytotoxicity but kept their full microtubule binding affinity, and all induced lattice expansion upon binding. Additional nuclear magnetic resonance studies propose that Taxol binds to a small fraction of straight tubulin present in solution. Our results suggest a mode of action of Taxol, where the core structure is responsible for the interacting energy while the bulky hydrophobic C13 side chain enables binding selectively to straight tubulin and promotes stabilization.

scholarly journals An effect of side chain length on the solution structure of poly(9,9-dialkylfluorene)s in toluene

Polymer ◽  
2008 ◽  
Vol 49 (8) ◽  
pp. 2033-2038 ◽  
Author(s):  
M. Knaapila ◽  
L. Almásy ◽  
V.M. Garamus ◽  
M.L. Ramos ◽  
L.L.G. Justino ◽  
...  
Keyword(s):  
Chain Length ◽  
Solution Structure ◽  
Side Chain ◽  
Side Chain Length
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