Folding of the polypeptide chain(s), conformational flexibility and reactivity of the metal active site of hemocyanin and tyrosinase

1990 ◽  
Vol 3 (2) ◽  
pp. 93-97 ◽  
Author(s):  
Mariano Beltramini ◽  
Meri Santamaria ◽  
Benedetto Salvato ◽  
Konrad Lerche
Keyword(s):  
Active Site ◽  
Polypeptide Chain ◽  
Conformational Flexibility

On the Role of the Conformational Flexibility of the Active-site Lid on the Allosteric Kinetics of Glucosamine-6-phosphate Deaminase

2002 ◽  
Vol 319 (1) ◽  
pp. 183-189 ◽  
Author(s):  
Ismael Bustos-Jaimes ◽  
Alejandro Sosa-Peinado ◽  
Enrique Rudiño-Piñera ◽  
Eduardo Horjales ◽  
Mario L. Calcagno
Keyword(s):  
Active Site ◽  
Conformational Flexibility ◽  
Kinetics Of

scholarly journals Intraresidual Correlated Motions in Peptide Chain

2019 ◽  
Author(s):  
Adolfo Bastida ◽  
Javier Carmona-García ◽  
José Zúñiga ◽  
Alberto Requena ◽  
Javier Cerezo
Keyword(s):  
Molecular Dynamics ◽  
Polypeptide Chain ◽  
Conformational Flexibility ◽  
Peptide Chain ◽  
Atomic Displacements ◽  
Correlated Motions ◽  
Polypeptide Chains

Conformational flexibility of polypeptide chains is mainly driven by changes in the (phi, psi) dihedrals of each residue. Such motions, however, are not completely independent, as certain (anti)correlated motions are favored. In this work, we investigate the correlations between the dihedral displacements of adjacent residues, (Δphi i, Δpsi i+1) and (Δphi i-1, Δpsi i), i.e. interresidual, and within the same residue, (Δphi i, Δpsi i), i.e. intraresidual, by analyzing extensive Molecular Dynamics trajectories of initially extended polyalanine chains in detail. Correlations are evaluated individually at different residue conformations covering the whole (phi, psi)-space. From these we draw maps which clearly show how the coupled motions strongly depend on the conformation, thus unveiling an unprecedented strong intramolecular correlation displaying opposite (correlated/anticorrelated) behaviors at different conformations. By developing a tailored model, it is also demonstrated that both inter and intraresidual correlations arise from the propensity of the peptide to minimize the overall atomic displacements along the whole polypeptide chain.

scholarly journals Conformational Flexibility and the Interaction of Huperzine A in the Active Site of Acetylcholinesterase: A Quantum Chemical and Charge Density Study

2016 ◽  
Author(s):  
Renuga Parameswari Azhagesan ◽  
Saravanan Kandasamy ◽  
Kumaradhas Poomani
Keyword(s):  
Molecular Docking ◽  
Density Distribution ◽  
Charge Density ◽  
Gas Phase ◽  
Active Site ◽  
Quantum Chemical ◽  
Conformational Flexibility ◽  
Huperzine A ◽  
Charge Density Distribution ◽  
Density Analysis

Huperzine A is an herbal reversible inhibitor of Acetylcholinesterase (AChE). A molecular docking analysis on Huperzine A molecule has been carried out to understand its structure, conformational flexibility, intermolecular interaction and the binding affinity in the active site of AChE enzyme. Further, the charge density distribution of huperzine A molecule (lifted from the active site of AChE) was determined from the high level quantum chemical calculations coupled with charge density analysis. The binding affinity of Huperzine A towards AChE was calculated from the molecular docking; the lowest docked energy is -8.46 kcal/mol. In the active site, huperzine A molecule interacts with acyl binding pocket-Phe330 of AChE, that is, the bicyclo ring group of huperzine A forms an intermolecular interaction with the oxygen atom of main chain of the amino acid residue Phe330 at the distances 3.02 and 3.25 Å respectively. On the other hand, a gas phase study on huperzine A molecule also performed using HF and DFT (B3LYP) methods with the basis set 6-311G**. The molecular structure, conformation, and the charge density distribution of huperzine A molecule in the gas phase have determined using quantum chemical calculations and the charge density analysis. The comparative studies between the gas phase and the active site forms of huperzine A molecule, explicitly reveals the degree of conformational modification and the charge density redistribution of huperzine A when present in the active site. The dipole moment of the molecule in the active site is 6.85 D, which is slightly higher than its gas phase value (5.91 D). The electrostatic potential (ESP) surface of active site molecule clearly shows the strong electronegative and positive ESP regions of the molecule, which are the expected strong reactive locations of the molecule.

Modulation of the Rcs-mediated signal transfer by conformational flexibility

2008 ◽  
Vol 36 (6) ◽  
pp. 1427-1432 ◽  
Author(s):  
Vladimir V. Rogov ◽  
Kerstin Schmöe ◽  
Fank Löhr ◽  
Natalia Yu. Rogova ◽  
Frank Bernhard ◽  
...  
Keyword(s):  
Active Site ◽  
Regulatory Networks ◽  
Helical Structure ◽  
Conformational Flexibility ◽  
Conformational Exchange ◽  
Phosphoryl Transfer ◽  
Phosphate Binding ◽  
Signal Transfer ◽  
Sensor Kinases ◽  
The Individual

The Rcs (regulator of capsule synthesis) signalling complex comprises the membrane-associated hybrid sensor kinases RcsC and RcsD, the transcriptional regulator RcsB and the two co-inducers RcsA and RcsF. Acting as a global regulatory network, the Rcs phosphorelay controls multiple cellular pathways including capsule synthesis, cell division, motility, biofilm formation and virulence mechanisms. Signal-dependent communication of the individual Rcs domains showing histidine kinase, phosphoreceiver, phosphoryl transfer and DNA-binding activities is characteristic and essential for the modulation of signal transfer. We have analysed the structures of core elements of the Rcs network including the RcsC-PR (phosphoreceiver domain of RcsC) and the RcsD-HPt (histidine phosphotransfer domain of RcsD), and we have started to characterize the dynamics and recognition mechanisms of the proteins. RcsC-PR represents a typical CheY-like α/β/α sandwich fold and it shows a large conformational flexibility near the active-site residue Asp875. NMR analysis revealed that RcsC-PR is able to adopt preferred conformations upon Mg2+ co-ordination, BeF3− activation, phosphate binding and RcsD-HPt recognition. In contrast, the α-helical structure of RcsD-HPt is conformationally stable and contains a recognition area in close vicinity to the active-site His842 residue. Our studies indicate the importance of protein dynamics and conformational exchange for the differential response to the variety of signals perceived by complex regulatory networks.

Oxidation by 2-oxoglutarate oxygenases: non-haem iron systems in catalysis and signalling

2005 ◽  
Vol 363 (1829) ◽  
pp. 807-828 ◽  
Author(s):  
K.S Hewitson ◽  
N Granatino ◽  
R.W.D Welford ◽  
M.A McDonough ◽  
C.J Schofield
Keyword(s):  
Active Site ◽  
Ferrous Iron ◽  
Substrate Oxidation ◽  
Conformational Flexibility ◽  
Side Chain ◽  
Oxidative Decarboxylation ◽  
Structural Studies ◽  
Wide Range ◽  
Ferryl Species ◽  
Haem Iron

The 2-oxoglutarate (2OG) and ferrous iron dependent oxygenases are a superfamily of enzymes that catalyse a wide range of reactions including hydroxylations, desaturations and oxidative ring closures. Recently, it has been discovered that they act as sensors in the hypoxic response in humans and other animals. Substrate oxidation is coupled to conversion of 2OG to succinate and carbon dioxide. Kinetic, spectroscopic and structural studies are consistent with a consensus mechanism in which ordered binding of (co)substrates enables control of reactive intermediates. Binding of the substrate to the active site triggers the enzyme for ligation of dioxygen to the metal. Oxidative decarboxylation of 2OG then generates the ferryl species thought to mediate substrate oxidation. Structural studies reveal a conserved double-stranded β-helix core responsible for binding the iron, via a 2His-1carboxylate motif and the 2OG side chain. The rigidity of this core contrasts with the conformational flexibility of surrounding regions that are involved in binding the substrate. Here we discuss the roles of 2OG oxygenases in terms of the generic structural and mechanistic features that render the 2OG oxygenases suited for their functions.

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