scholarly journals Dynamic Folding Pathway Models of the Trp-Cage Protein

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
In-Ho Lee ◽  
Seung-Yeon Kim
Keyword(s):  
Hydrogen Bonds ◽  
Conformational Changes ◽  
Early Stage ◽  
Side Chain ◽  
Folding Pathway ◽  
Hydrophobic Core ◽  
Native Structure ◽  
Pathway Models ◽  
Highly Correlated ◽  
Dynamic Folding

Using action-derived molecular dynamics (ADMD), we study the dynamic folding pathway models of the Trp-cage protein by providing its sequential conformational changes from its initial disordered structure to the final native structure at atomic details. We find that the numbers of native contacts and native hydrogen bonds are highly correlated, implying that the native structure of Trp-cage is achieved through the concurrent formations of native contacts and native hydrogen bonds. In early stage, an unfolded state appears with partially formed native contacts (~40%) and native hydrogen bonds (~30%). Afterward, the folding is initiated by the contact of the side chain of Tyr3 with that of Trp6, together with the formation of the N-terminalα-helix. Then, the C-terminal polyproline structure docks onto the Trp6 and Tyr3 rings, resulting in the formations of the hydrophobic core of Trp-cage and its near-native state. Finally, the slow adjustment processes of the near-native states into the native structure are dominant in later stage. The ADMD results are in agreement with those of the experimental folding studies on Trp-cage and consistent with most of other computational studies.

scholarly journals Comparative Assessment of NMR Probes for the Experimental Description of Protein Folding Pathways with High-Pressure NMR

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 656
Author(s):  
Vincent Van Deuren ◽  
Yin-Shan Yang ◽  
Karine de Guillen ◽  
Cécile Dubois ◽  
Catherine Anne Royer ◽  
...  
Keyword(s):  
High Pressure ◽  
Staphylococcal Nuclease ◽  
Comparative Assessment ◽  
Side Chain ◽  
Folding Pathway ◽  
Hydrophobic Core ◽  
Folding Pathways ◽  
Partial Unfolding ◽  
Protein Folding Pathways ◽  
Similar Description

Multidimensional NMR intrinsically provides multiple probes that can be used for deciphering the folding pathways of proteins: NH amide and CH groups are strategically located on the backbone of the protein, while CH3 groups, on the side-chain of methylated residues, are involved in important stabilizing interactions in the hydrophobic core. Combined with high hydrostatic pressure, these observables provide a powerful tool to explore the conformational landscapes of proteins. In the present study, we made a comparative assessment of the NH, CH, and CH3 groups for analyzing the unfolding pathway of ∆+PHS Staphylococcal Nuclease. These probes yield a similar description of the folding pathway, with virtually identical thermodynamic parameters for the unfolding reaction, despite some notable differences. Thus, if partial unfolding begins at identical pressure for these observables (especially in the case of backbone probes) and concerns similar regions of the molecule, the residues involved in contact losses are not necessarily the same. In addition, an unexpected slight shift toward higher pressure was observed in the sequence of the scenario of unfolding with CH when compared to amide groups.

scholarly journals Dynamic folding pathway models of the villin headpiece subdomain (HP-36) structure

2010 ◽  
Vol 31 (1) ◽  
pp. 57-65 ◽  
Author(s):  
In-Ho Lee ◽  
Seung-Yeon Kim ◽  
Jooyoung Lee
Keyword(s):  
Folding Pathway ◽  
Villin Headpiece ◽  
Pathway Models ◽  
Dynamic Folding

scholarly journals Major conformational changes in the structure of lysozyme obtained from a crystal with a very low solvent content

2019 ◽  
Vol 75 (11) ◽  
pp. 687-696
Author(s):  
M. Carmen Salinas-Garcia ◽  
Marina Plaza-Garrido ◽  
Daniel Alba-Elena ◽  
Ana Camara-Artigas
Keyword(s):  
Conformational Changes ◽  
Crystal Form ◽  
Catalytic Site ◽  
Side Chain ◽  
Hydrophobic Core ◽  
Orthorhombic Space Group ◽  
Solvent Content ◽  
Cell Parameters ◽  
Saccharide Binding ◽  
Α Helix

A new crystal form of lysozyme with a very low solvent content (26.35%) has been obtained in the orthorhombic space group P212121 (with unit-cell parameters a = 30.04, b = 51.68, c = 61.53 Å). The lysozyme structure obtained from these crystals does not show the typical overall fold. Instead, major conformational changes take place in some elements of the secondary structure and in the hydrophobic core of the protein. At the end of the central α-helix (α2), Glu35 is usually buried in the catalytic site and shows an abnormally high pK a value, which is key to the activity of the enzyme. The high pK a value of this glutamate residue is favoured by the hydrophobic environment, particularly by its neighbour Trp108, which is important for structural stability and saccharide binding. In this new structure, Trp108 shows a 90° rotation of its side chain, which results in the rearrangement of the hydrophobic core. Conformational changes also result in the exposure of Glu35 to the solvent, which impairs the catalytic site by increasing the distance between Glu35 and Asp52 and lowering the pK a value of the glutamate. Altogether, this new lysozyme structure reveals major conformational changes in the hydrophobic core and catalytic site that might play a role in the folding and bactericidal function of the protein.

Dynamic folding pathway models of α-helix and β-hairpin structures

2005 ◽  
Vol 412 (4-6) ◽  
pp. 307-312 ◽  
Author(s):  
In-Ho Lee ◽  
Seung-Yeon Kim ◽  
Jooyoung Lee
Keyword(s):  
Folding Pathway ◽  
Pathway Models ◽  
Hairpin Structures ◽  
Α Helix ◽  
Dynamic Folding

scholarly journals Hydrophobic Core Mutations in CI2 Globally Perturb Fast Side-Chain Dynamics Similarly without Regard to Position†

Biochemistry ◽  
2008 ◽  
Vol 47 (33) ◽  
pp. 8566-8576 ◽  
Author(s):  
Matthew J. Whitley ◽  
Jun Zhang ◽  
Andrew L. Lee
Keyword(s):  
Side Chain ◽  
Hydrophobic Core ◽  
Chain Dynamics ◽  
Side Chain Dynamics

scholarly journals Route, mechanism, and implications of proton import during Na+/K+ exchange by native Na+/K+-ATPase pumps

2014 ◽  
Vol 143 (4) ◽  
pp. 449-464 ◽  
Author(s):  
Natascia Vedovato ◽  
David C. Gadsby
Keyword(s):  
Binding Site ◽  
Single Molecule ◽  
Conformational Changes ◽  
Outward Current ◽  
Side Chain ◽  
Ion Binding ◽  
Inward Current ◽  
Na Release ◽  
K Transport ◽  
External K

A single Na+/K+-ATPase pumps three Na+ outwards and two K+ inwards by alternately exposing ion-binding sites to opposite sides of the membrane in a conformational sequence coupled to pump autophosphorylation from ATP and auto-dephosphorylation. The larger flow of Na+ than K+ generates outward current across the cell membrane. Less well understood is the ability of Na+/K+ pumps to generate an inward current of protons. Originally noted in pumps deprived of external K+ and Na+ ions, as inward current at negative membrane potentials that becomes amplified when external pH is lowered, this proton current is generally viewed as an artifact of those unnatural conditions. We demonstrate here that this inward current also flows at physiological K+ and Na+ concentrations. We show that protons exploit ready reversibility of conformational changes associated with extracellular Na+ release from phosphorylated Na+/K+ pumps. Reversal of a subset of these transitions allows an extracellular proton to bind an acidic side chain and to be subsequently released to the cytoplasm. This back-step of phosphorylated Na+/K+ pumps that enables proton import is not required for completion of the 3 Na+/2 K+ transport cycle. However, the back-step occurs readily during Na+/K+ transport when external K+ ion binding and occlusion are delayed, and it occurs more frequently when lowered extracellular pH raises the probability of protonation of the externally accessible carboxylate side chain. The proton route passes through the Na+-selective binding site III and is distinct from the principal pathway traversed by the majority of transported Na+ and K+ ions that passes through binding site II. The inferred occurrence of Na+/K+ exchange and H+ import during the same conformational cycle of a single molecule identifies the Na+/K+ pump as a hybrid transporter. Whether Na+/K+ pump–mediated proton inflow may have any physiological or pathophysiological significance remains to be clarified.

scholarly journals Phosphate-Catalyzed Succinimide Formation from an NGR-Containing Cyclic Peptide: A Novel Mechanism for Deammoniation of the Tetrahedral Intermediate

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2217 ◽  
Author(s):  
Ryota Kirikoshi ◽  
Noriyoshi Manabe ◽  
Ohgi Takahashi
Keyword(s):  
Conformational Changes ◽  
Density Functional ◽  
Cyclic Peptide ◽  
Density Functional Theory Method ◽  
Proton Exchange ◽  
Computational Method ◽  
Side Chain ◽  
Tetrahedral Intermediate ◽  
Rate Determining Step ◽  
Proton Source

Spontaneous deamidation in the Asn-Gly-Arg (NGR) motif that yields an isoAsp-Gly-Arg (isoDGR) sequence has recently attracted considerable attention because of the possibility of application to dual tumor targeting. It is well known that Asn deamidation reactions in peptide chains occur via the five-membered ring succinimide intermediate. Recently, we computationally showed by the B3LYP density functional theory method, that inorganic phosphate and the Arg side chain can catalyze the NGR deamidation using a cyclic peptide, c[CH2CO–NGRC]–NH2. In this previous study, the tetrahedral intermediate of the succinimide formation was assumed to be readily protonated at the nitrogen originating from the Asn side chain by the solvent water before the release of an NH3 molecule. In the present study, we found a new mechanism for the decomposition of the tetrahedral intermediate that does not require the protonation by an external proton source. The computational method is the same as in the previous study. In the new mechanism, the release of an NH3 molecule occurs after a proton exchange between the peptide and the phosphate and conformational changes. The rate-determining step of the overall reaction course is the previously reported first step, i.e., the cyclization to form the tetrahedral intermediate.

scholarly journals Diethyl (E)-2,3-bis[(E)-(2-methyl-2-phenylhydrazin-1-ylidene)methyl]but-2-enedioate

2014 ◽  
Vol 70 (6) ◽  
pp. o723-o723
Author(s):  
Peng Liu ◽  
Libin Yuan ◽  
Xiuqing Song ◽  
Hong Yan
Keyword(s):  
Hydrogen Bonds ◽  
Title Compound ◽  
Phenyl Ring ◽  
Side Chain ◽  
Dihedral Angles ◽  
Inversion Symmetry ◽  
Compound C ◽  
Corrugated Sheets ◽  
Major Conformation

The complete molecule of the title compound, C24H28N4O4, is generated by crystallographic inversion symmetry. The ethyl side chain is disordered over two sets of sites in a 0.57 (4):0.43 (4) ratio. The dihedral angles between the methylidene group and the phenyl ring and ester side chain (major conformation) are 7.61 (8) and 86.95 (8)°, respectively. In the crystal, molecules are linkedviaC—H...O hydrogen bonds, forming corrugated sheets lying parallel to (010).

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