pH-dependent structural changes in haemoglobin component V from the midge larvaPropsilocerus akamusi(Orthocladiinae, Diptera)

2010 ◽  
Vol 66 (3) ◽  
pp. 258-267 ◽  
Author(s):  
Takao Kuwada ◽  
Tomokazu Hasegawa ◽  
Takashi Takagi ◽  
Isamu Sato ◽  
Fumio Shishikura
Keyword(s):  
Functional Properties ◽  
Structural Changes ◽  
Ph Dependence ◽  
Oxygen Affinity ◽  
Side Chain ◽  
Ligand Molecule ◽  
Distal Side ◽  
Ph Conditions ◽  
Ph Dependent ◽  
Dependent Behaviour

Haemoglobin component V (Hb V) from the midge larvaPropsilocerus akamusiexhibits oxygen affinity despite the replacement of HisE7 and a pH-dependence of its functional properties. In order to understand the contribution of the distal residue to the ligand-binding properties and the pH-dependent structural changes in this insect Hb, the crystal structure of Hb V was determined under five different pH conditions. Structural comparisons of these Hb structures indicated that at neutral pH ArgE10 contributes to the stabilization of the haem-bound ligand molecule as a functional substitute for the nonpolar E7 residue. However, ArgE10 does not contribute to stabilization at acidic and alkaline pH because of the swinging movement of the Arg side chain under these conditions. This pH-dependent behaviour of Arg results in significant differences in the hydrogen-bond network on the distal side of the haem in the Hb V structures at different pH values. Furthermore, the change in pH results in a partial movement of the F helix, considering that coupled movements of ArgE10 and the F helix determine the haem location at each pH. These results suggested that Hb V retains its functional properties by adapting to the structural changes caused by amino-acid replacements.

scholarly journals Systematic exploration of the pH dependence of a peptide hydrogel

2019 ◽  
Vol 97 (6) ◽  
pp. 430-434 ◽  
Author(s):  
Natashya Falcone ◽  
Tsuimy Shao ◽  
Xiaoyi Sun ◽  
Heinz-Bernhard Kraatz
Keyword(s):  
Mechanical Strength ◽  
Narrow Range ◽  
Ph Dependence ◽  
Stimuli Responsive ◽  
Systematic Exploration ◽  
Ph Conditions ◽  
Ph Dependent ◽  
Functional Biomaterials ◽  
Peptide Hydrogel

Stimuli-responsive peptide gels are a growing class of functional biomaterials that are involved in many applications in research. Here, we present a novel di-peptide hydrogel from the compound Boc–Phe–Trp–OH in various buffer and pH conditions. We examine the effects of different stimuli, including temperature and pH, on the mechanical strength of the gels through frequency rheology studies. We found that this hydrogelator is highly pH dependent, only forming a gel in a narrow range of pH 6–7. This hydrogelator hold promise for the development of new stimuli-responsive biomaterials for specific applications that require this type of specific stimuli.

Effects of heme modification on oxygen affinity and cooperativity of human adult hemoglobin

2015 ◽  
Vol 19 (01-03) ◽  
pp. 301-307 ◽  
Author(s):  
Tomokazu Shibata ◽  
Eisuke Furuichi ◽  
Kiyohiro Imai ◽  
Akihiro Suzuki ◽  
Yasuhiko Yamamoto
Keyword(s):  
Structural Changes ◽  
Oxygen Affinity ◽  
Side Chain ◽  
Side Chains ◽  
Human Adult ◽  
Alkaline Transition ◽  
Functional Control ◽  
Adult Hemoglobin ◽  
The Relationship ◽  
Heme Cofactor

We substituted strongly electron-withdrawing trifluoromethyl ( CF 3) group(s) as heme side chain(s) of human adult hemoglobin (Hb) to achieve large alterations of the heme electronic structure, in order to elucidate the relationship between the oxygen ( O 2) binding properties of Hb and the electronic properties of heme peripheral side chains. The obtained results were compared with those of similar studies performed on myoglobin (Mb), e.g. (Nishimura R, Matsumoto D, Shibata T, Yanagisawa S, Ogura T, Tai H, Matsuo T, Hirota S, Neya S, Suzuki A, and Yamamoto Y. Inorg. Chem. 2014; 53: 9156–9165). These two proteins shared the common feature of a decrease in O 2 affinity upon the CF 3 substitution(s). Using the P50 value, which is the partial pressure of O 2 required for 50% oxygenation of a protein, and the equilibrium constant ( p K a ) of the "acid-alkaline transition" in the met form of a protein as measures of the O 2 affinity and the electron density of heme Fe atom of the protein, respectively, a linear p K a - log (1/P50) relationship was demonstrated for the Hb and Mb systems. The native Hb, however, deviated from the p K a - log (1/P50) relationship, while the native Mb followed it. These results highlighted the significance of the vinyl side chains of the heme cofactor in the functional control of Hb through tertiary and quaternary structural changes upon the oxygenation of the protein.

scholarly journals pH-controlled stacking direction of the β-strands in peptide fibrils

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Wei-Hsuan Tseng ◽  
Szu-Hua Chen ◽  
Hirotsugu Hiramatsu
Keyword(s):  
Structural Changes ◽  
Ph Dependence ◽  
Subsequent Formation ◽  
Generating Functional ◽  
Acidic Conditions ◽  
Β Sheets ◽  
Ph Dependent ◽  
Peptide Fibrils ◽  
Β Sheet ◽  
Self Aggregation

AbstractPeptides provide a framework for generating functional biopolymers. In this study, the pH-dependent structural changes in the 21–29 fragment peptide of β2-microglobulin (β2m21–29) during self-aggregation, i.e., the formation of an amyloid fibril, were discussed. The β-sheet structures formed during parallel stacking under basic conditions (pH ≥ 7.7) adopted an anti-parallel stacking configuration under acidic conditions (pH ≤ 7.6). The parallel and anti-parallel β-sheets existed separately at the intermediate pH (pH = 7.6–7.7). These results were attributed to the rigidity of the β-sheets in the fibrils, which prevented the stable hydrogen bonding interactions between the parallel and anti-parallel β-sheet moieties. This observed pH dependence was ascribed to two phenomena: (i) the pH-dependent collapse of the β2m21–29 fibrils, which consisted of 16 ± 3 anti-parallel β-sheets containing a total of 2000 β-strands during the deprotonation of the NH3+ group (pKa = 8.0) of the β-strands that occurred within 0.7 ± 0.2 strands of each other and (ii) the subsequent formation of the parallel β-sheets. We propose a framework for a functional biopolymer that could alternate between the two β-sheet structures in response to pH changes.

Rationalizing the pH-Activity Response for Escherichia Coli’s Glycinamide Ribonucleotidetransformylase Through Computational Methods

2019 ◽  
Author(s):  
Adrian Roitberg ◽  
Pancham Lal Gupta
Keyword(s):  
Transfer Reaction ◽  
Catalytic Mechanism ◽  
Ph Dependence ◽  
Ph Effects ◽  
Dependent Manner ◽  
E Coli ◽  
Gar Tfase ◽  
Activity Curve ◽  
Ph Dependent ◽  
Formyl Transfer

<div>Human Glycinamide ribonucleotide transformylase (GAR Tfase), a regulatory enzyme in the de novo purine biosynthesis pathway, has been established as an anti-cancer target. GAR Tfase catalyzes the formyl transfer reaction from the folate cofactor to the GAR ligand. In the present work, we study E. coli GAR Tfase, which has high sequence similarity with the human GAR Tfase with most functional residues conserved. E. coli GAR Tfase exhibits structural changes and the binding of ligands that varies with pH which leads to change the rate of the formyl transfer reaction in a pH-dependent manner. Thus, the inclusion of pH becomes essential for the study of its catalytic mechanism. Experimentally, the pH-dependence of the kinetic parameter kcat is measured to evaluate the pH-range of enzymatic activity. However, insufficient information about residues governing the pH-effects on the catalytic activity leads to ambiguous assignments of the general acid and base catalysts and consequently its catalytic mechanism. In the present work, we use pH-replica exchange molecular dynamics (pH-REMD) simulations to study the effects of pH on E. coli GAR Tfase enzyme. We identify the titratable residues governing the pH-dependent conformational changes in the system. Furthermore, we filter out the protonation states which are essential in maintaining the structural integrity, keeping the ligands bound and assisting the catalysis. We reproduce the experimental pH-activity curve by computing the population of key protonation states. Moreover, we provide a detailed description of residues governing the acidic and basic limbs of the pH-activity curve.</div>

Physicochemical and pH-dependent functional properties of proteins isolated from eight traditional Chinese beans

2021 ◽  
Vol 112 ◽  
pp. 106288 ◽  
Author(s):  
Jiao Ge ◽  
Cui-Xia Sun ◽  
Analucia Mata ◽  
Harold Corke ◽  
Ren-You Gan ◽  
...  
Keyword(s):  
Functional Properties ◽  
Ph Dependent

scholarly journals Structure-Activity Relationships of Sandalwood Odorants: Synthesis of a New Campholene Derivative

2010 ◽  
Vol 5 (9) ◽  
pp. 1934578X1000500
Author(s):  
Iris Stappen ◽  
Joris Höfinghoff ◽  
Gerhard Buchbauer ◽  
Peter Wolschann
Keyword(s):  
Structural Changes ◽  
Great Influence ◽  
Complete Loss ◽  
Side Chain ◽  
Side Chains ◽  
Quaternary Carbon ◽  
Structural Modifications ◽  
Structure Activity ◽  
Highly Sensitive ◽  
Sandalwood Odorants

Structural modifications of natural (-)-( Z)-β-santalol have shown that the sandalwood odor impression is highly sensitive, even to small structural changes. Particularly, the substitution of the quaternary carbon is of great influence on the scent. Epi-compounds with side chains in the endo-position possess sandalwood odor in only a few derivatives, whereas modifications at this side chain, as well as modification at the bicyclic ring systems mostly lead to a complete loss of sandalwood fragrance.

scholarly journals Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding

2008 ◽  
Vol 183 (5) ◽  
pp. 865-879 ◽  
Author(s):  
Christian Frantz ◽  
Gabriela Barreiro ◽  
Laura Dominguez ◽  
Xiaoming Chen ◽  
Robert Eddy ◽  
...  
Keyword(s):  
Actin Filament ◽  
Structural Changes ◽  
Ph Sensor ◽  
Ph Sensitive ◽  
Actin Binding ◽  
Filamentous Actin ◽  
Filament Dynamics ◽  
Ph Dependent ◽  
Dynamics Simulations

Newly generated actin free barbed ends at the front of motile cells provide sites for actin filament assembly driving membrane protrusion. Growth factors induce a rapid biphasic increase in actin free barbed ends, and we found both phases absent in fibroblasts lacking H+ efflux by the Na-H exchanger NHE1. The first phase is restored by expression of mutant cofilin-H133A but not unphosphorylated cofilin-S3A. Constant pH molecular dynamics simulations and nuclear magnetic resonance (NMR) reveal pH-sensitive structural changes in the cofilin C-terminal filamentous actin binding site dependent on His133. However, cofilin-H133A retains pH-sensitive changes in NMR spectra and severing activity in vitro, which suggests that it has a more complex behavior in cells. Cofilin activity is inhibited by phosphoinositide binding, and we found that phosphoinositide binding is pH-dependent for wild-type cofilin, with decreased binding at a higher pH. In contrast, phosphoinositide binding by cofilin-H133A is attenuated and pH insensitive. These data suggest a molecular mechanism whereby cofilin acts as a pH sensor to mediate a pH-dependent actin filament dynamics.

scholarly journals Adult and fetal haemoglobin J-Sardegna [α50(CE8)His→Asp]: functional and molecular modelling studies

2000 ◽  
Vol 346 (1) ◽  
pp. 193-199 ◽  
Author(s):  
Marcella CORDA ◽  
Maria C. DE ROSA ◽  
Maria G. PELLEGRINI ◽  
Maria T. SANNA ◽  
Alessandra OLIANAS ◽  
...  
Keyword(s):  
Functional Properties ◽  
Computational Modelling ◽  
Oxygen Affinity ◽  
Oxygen Binding ◽  
Structural Level ◽  
Fetal Haemoglobin ◽  
Significant Difference ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
2,3 Dpg

Haemoglobin (Hb) J-Sardegna [α50(CE8)His → Asp] is a haemoglobin variant characteristic of subjects from the island of Sardinia. Here we report a study of the functional properties of both fetal and adult Hb J-Sardegna. The results indicate that adult Hb J-Sardegna displays an oxygen affinity that is higher than that of adult Hb only in the presence of 2,3-diphosphoglycerate (2,3-DPG). On the contrary, at 20 °C, the oxygen affinity of fetal Hb J-Sardegna is identical to that of normal fetal haemoglobin, both in the presence and in the absence of 2,3-DPG. A significant difference between these two systems (i.e. a higher oxygen affinity of fetal Hb J-Sardegna) shows up very clearly only when temperature is increased to 37 °C. Hence in fetal Hb, the main effect of the amino acid substitution is a decrease in the overall enthalpy change of oxygenation. The results outline the role of the α1-β1 interface in assessing the thermodynamics of oxygen binding. The functional properties of both adult and fetal Hb J-Sardegna have been interpreted at the structural level in light of the results obtained by a computational modelling approach performed in comparison with HbA and Hb Aichi, a variant characterized by a different mutation [α50(CE8)His → Arg] at the same position.

Enhanced Analytic Approach for Describing pH Triggered Fast Drug Release Systems

2021 ◽  
Vol 18 ◽  
Author(s):  
Aykut Elmas ◽  
Guliz Akyuz ◽  
Ayhan Bergal ◽  
Muberra Andac ◽  
Omer Andac
Keyword(s):  
Drug Release ◽  
Ph Dependence ◽  
Slope Angle ◽  
Ph Sensitive ◽  
Analytic Model ◽  
Two Dimensional ◽  
Analytic Equation ◽  
One Dimensional ◽  
Ph Dependent ◽  
Fast Release

Background: pH sensitive dendrimers attached to nanocarriers, as one of the drug release systems, has become quite popular due to their ease of manufacture in experimental conditions and ability to generate fast drug release in the targeted area. This kind of fast release behavior cannot be represented properly most of the existing kinetic mathematical models. Besides, these models have either no pH dependence or pH dependence added separately. So, they have remained one dimensional. Objective: The aim of this study was to establish the proper analytic equation to describe the fast release of drugs from pH sensitive nanocarrier systems. Then, to combine it with the pH dependent equation for establishing a two-dimensional model for whole system. Methods: We used four common kinetic models for comparison and we fitted them to the release data. Finding that, only Higuchi and Korsmeyer-Peppas models show acceptable fit results. None of these models have pH dependence. To get a better description for pH triggered fast release, we observed the behavior of the slope angle of the release curve. Then we puroposed a new analytic equation by using relation between the slope angle and time. Result: To add a pH dependent equation, we assumed the drug release is “on” or “off” above/below specific pH value and we modified a step function to get a desired behavior. Conclusion: Our new analytic model shows good fitting, not only one-dimensional time dependent release, but also two-dimensional pH dependent release, that provides a useful analytic model to represent release profiles of pH sensitive fast drug release systems.

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