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.

scholarly journals Structural and functional effects of selective chemical modifications of Scapharca inaequivalvis haemoglobins in relation to their unique assembly

1987 ◽  
Vol 241 (2) ◽  
pp. 499-504 ◽  
Author(s):  
A Boffi ◽  
M Gattoni ◽  
R Santucci ◽  
P Vecchini ◽  
F Ascoli ◽  
...  
Keyword(s):  
Functional Properties ◽  
Oxygen Affinity ◽  
Thiol Group ◽  
Cysteine Residue ◽  
Oxygen Binding ◽  
Thiol Groups ◽  
Functional Roles ◽  
Dimeric Unit ◽  
Structural And Functional Properties ◽  
Thiol Reagent

The structural and functional roles of lysyl and thiol groups in the dimeric (HbI) and tetrameric (HbII) haemoglobins from the mollusc Scapharca inaequivalvis have been assessed. In these haemoglobins a unique mode of assembly (the haem-carrying E and F helices form the intersubunit contact of the dimeric unit) is associated with co-operative oxygen binding. Extensive acylation is accompanied by significant haem oxidation. Modification of one or two lysyl residues per chain (corresponding to approximately 20% of the total residues) does not affect the structural and functional properties of both haemoglobins, in line with the proposal that the intersubunit contacts are rich in hydrophobic residues. The modification of the thiol groups does not influence the state of association in both HbI and HbII, despite the location of the cysteine residue common to all polypeptide chains in the vicinity of the major intersubunit contact. The effect on the functional properties depends on the size of the thiol reagent: p-chloromercuribenzoate and phenylmercuric acetate increase the oxygen affinity about 20-fold, but iodoacetamide and mercuric chloride have no effect. Moreover, electrophoresis experiments indicate that p-chloromercuribenzoate is bound in a co-operative fashion, the degree of co-operativity being much higher in the dimeric HbI. Thus, only in HbII are intermediates containing substoichiometric amounts of p-chloromercuribenzoate formed in significant amounts. Their oxygen binding properties show that reaction of only one thiol group/tetramer suffices to alter the oxygen affinity of the molecule.

scholarly journals ALLOSTERIC CONTROL OF OXYGEN BINDING BY HAEMOGLOBIN DURING EMBRYONIC DEVELOPMENT IN THE CROCODILE CROCODYLUS POROSUS: THE ROLE OF RED CELL ORGANIC PHOSPHATES AND CARBON DIOXIDE

1993 ◽  
Vol 175 (1) ◽  
pp. 15-32 ◽  
Author(s):  
G. C. Grigg ◽  
R. M. G. Wells ◽  
L. A. Beard
Keyword(s):  
Embryonic Development ◽  
Whole Blood ◽  
Marked Effect ◽  
Oxygen Affinity ◽  
Oxygen Binding ◽  
Blood Oxygen ◽  
Embryonic Life ◽  
Crocodylus Porosus ◽  
Blood Oxygen Affinity ◽  
2,3 Dpg

The P50 of whole blood [30°C, PCO2=2.08 kPa (15.6 mmHg)] decreases during embryonic development from approximately 6.7 kPa (50 mmHg) at 15 days to about half this value at hatching (86 days), paralleling a decrease in ATP from 100 to 5–10 micromole g-1 Hb. There is also a progressive changeover from embryonic to adult haemoglobin (HbA). A pulse of 2,3- diphosphoglycerate (2,3-DPG) (18 micromole g-1 Hb) occurs late in embryonic life. It has no effect on whole-blood oxygen-affinity and falls rapidly at hatching to values typical of post-hatchling crocodilians in general (<1.0 micromole g-1 Hb). ATP has a marked effect on the oxygen affinity of embryonic haemoglobin (HbE) but not on HbA. 2,3-DPG has only very small effects on the oxygen affinities of HbE and HbA. CO2 has a small effect on the oxygen affinity of HbE but a marked effect on that of HbA. Values of PO2 measured in the chorio-allantoic artery [2.9 kPa (22 mmHg)] and vein [5.9 kPa (52 mmHg)] imply an increase in saturation from approximately 30 % to more than 80 %. Neither whole-blood oxygen-affinity nor ATP level was altered in response to an experimental 7-day exposure to low ambient oxygen levels [10.7 kPa (80 mmHg)]. The results do not lend themselves easily to the pan-selectionist paradigm in which all physiological traits are viewed as being adaptive.

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

2000 ◽  
Vol 346 (1) ◽  
pp. 193 ◽  
Author(s):  
Marcella CORDA ◽  
Maria C. DE ROSA ◽  
Maria G. PELLEGRINI ◽  
Maria T. SANNA ◽  
Alessandra OLIANAS ◽  
...  
Keyword(s):  
Molecular Modelling ◽  
Fetal Haemoglobin ◽  
Molecular Modelling Studies ◽  
Modelling Studies

scholarly journals Hemoglobin Affinity for Oxygen in Chronic Renal Disease: The Effect of Hemodialysis

Blood ◽  
1974 ◽  
Vol 43 (3) ◽  
pp. 417-424 ◽  
Author(s):  
Marshall A. Lichtman ◽  
Marion S. Murphy ◽  
Barbara J. Byer ◽  
Richard B. Freeman
Keyword(s):  
Renal Disease ◽  
Base Excess ◽  
Chronic Renal Disease ◽  
Oxygen Affinity ◽  
Inorganic Phosphorus ◽  
Oxygen Binding ◽  
Red Cell ◽  
Highly Correlated ◽  
2,3 Dpg

Abstract The affinity of hemoglobin for oxygen may increase significantly in subjects who are hypophosphatemic and alkalotic. We studied the organic phosphate content and oxygen binding by hemoglobin of red cells in subjects undergoing hemodialysis, during which time a decrease in plasma inorganic phosphate and an increase in blood pH may occur. Red cell 2,3-DPG was not correlated with plasma inorganic phosphorus, whereas red cell ATP was highly correlated with plasma inorganic phosphorus when analyses were made on predialysis samples. Predialysis red cell inorganic phosphorus was highly correlated with plasma inorganic phosphorus, supporting the concept that intraerythrocytic inorganic phosphorus is maintained by a gradient from plasma to cell. Plasma inorganic phosphorus decreased by 45% during the period of hemodialysis, whereas red cell inorganic phosphorus did not change. Red cell 2,3-DPG, ATP, and oxygen binding by hemoglobin at standard conditions of temperature, pH, and pCO2 were not altered after 6 hr of hemodialysis. Plasma pH and base excess increased during dialysis. The increase in base excess, an estimate of the non-pH-dependent effect of CO2 on oxygen binding by hemoglobin, counterbalanced a portion of the effect of elevated pH on hemoglobin— oxygen affinity under in vivo conditions. Hence, only a slight increase in oxygen binding by hemoglobin occurred. Moreover, late dialysis symptoms were not associated with the degree of alkalosis or with the extent of change in hemoglobin’s affinity for oxygen. Red cell 2,3-DPG content was lower and hemoglobin’s affinity for oxygen was higher in subjects with chronic renal disease than in nonazotemic subjects with similar hemoglobin deficits. Moreover, increased red cell ATP in chronic renal disease patients did not influence oxygen binding by hemoglobin.

scholarly journals Circe's haemoglobins, pig–human hybrids: functional characterization and structural considerations

1998 ◽  
Vol 335 (2) ◽  
pp. 211-216 ◽  
Author(s):  
Maria T. SANNA ◽  
Bruno GIARDINA ◽  
Mariagiuseppina PELLEGRINI ◽  
Alessandra OLIANAS ◽  
Irene MESSANA ◽  
...  
Keyword(s):  
Thermodynamic Properties ◽  
Structural Properties ◽  
Functional Properties ◽  
Functional Characterization ◽  
Oxygen Affinity ◽  
Oxygen Binding ◽  
Β Chain

We report the isolation and the functional characterization of α and β chains from pig (Sus scropha domesticus) haemoglobin, as well as of the pig–human hybrid haemoglobins, α2hβ2p and α2pβ2h (i.e. Circe's haemoglobins), obtained by mixing the purified α and β pig chains respectively with the corresponding partner human chains. Their functional properties have been compared with those of both parental haemoglobins in order to obtain information on the role of the different subunits and of their inter-relationships, both at the structural and functional levels. The results indicate that the functional properties of both hybrids are closer to those of the parental haemoglobin that provides the β chains, confirming the major role of the β chains in determining the oxygen affinity and the modulation mechanisms of the tetrameric molecule. This is supported by the thermodynamic properties, since the very low ΔH of oxygen binding that characterizes pig haemoglobin and the α2hβ2p hybrid haemoglobin may be taken as the reflection of specific structural properties of pig β chain.

Quaternary structure of Limulus polyphemus hemocyanin

1978 ◽  
Vol 36 (2) ◽  
pp. 176-177
Author(s):  
T. Wichertjes ◽  
E.J. Kwak ◽  
E.F.J. Van Bruggen
Keyword(s):  
Electron Microscopy ◽  
Functional Properties ◽  
Horseshoe Crab ◽  
Temperature Jump ◽  
Quaternary Structure ◽  
Crystallographic Analysis ◽  
Limulus Polyphemus ◽  
Oxygen Binding ◽  
X Ray ◽  
Intact Molecule

Hemocyanin of the horseshoe crab (Limulus polyphemus) has been studied in nany ways. Recently the structure, dissociation and reassembly was studied using electron microscopy of negatively stained specimens as the method of investigation. Crystallization of the protein proved to be possible and X-ray crystallographic analysis was started. Also fluorescence properties of the hemocyanin after dialysis against Tris-glycine buffer + 0.01 M EDTA pH 8.9 (so called “stripped” hemocyanin) and its fractions II and V were studied, as well as functional properties of the fractions by NMR. Finally the temperature-jump method was used for assaying the oxygen binding of the dissociating molecule and of preparations of isolated subunits. Nevertheless very little is known about the structure of the intact molecule. Schutter et al. suggested that the molecule possibly consists of two halves, combined in a staggered way, the halves themselves consisting of four subunits arranged in a square.

Synthesis of Indolyl Pyrazole Scaffolds as Potential Anti-cancer Agents and their Molecular Modelling Studies

2020 ◽  
Vol 17 (7) ◽  
pp. 828-839
Author(s):  
Ganga Reddy Gaddam ◽  
Pramod Kumar Dubey ◽  
Venkata Ramana Reddy Chittireddy
Keyword(s):  
Cell Lines ◽  
Biological Activities ◽  
Moderate Activity ◽  
Lung Cancer Cell ◽  
Anti Cancer ◽  
A549 Lung Cancer Cell ◽  
New Chemical Entities ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
A549 Lung

Background:: Indole and pyrazoles are one of the prime structural units in the field of medicinal chemistry and have been reported to exhibit a variety of biological activities specifically anti-cancer. In view of their medicinal significance, we synthesized a conjugate of the two moieties to get access to newer and potential anti-cancer agents. Methods: Indolyl pyrazoles [3-(1,3-diphenyl-1H-pyrazol-4-yl)-2-(1-methyl-1H-indole-3-carbon yl)acrylonitriles] (4a-l) were synthesized by adopting simple and greener protocol and all the synthesized derivatives were docked against Bcl-2 protein and the selected chemical moieties were screened for their cytotoxicity by using the MTT assay. Results: : All the synthesized compounds were docked against BCL-2 protein in order to understand their binding pattern. Among the 12 compounds docked, 4d, 4f, 4h, 4j, and 4l compounds exhibited better protein binding interactions and the same were screened for their anti-cancer activity against A549 (lung) cancer cell lines at a concentration of 100 μM using Doxorubicin as standard. Substitutions such as N-benzyl, N-ethyl groups and halogen groups such as Br, Cl on indole ring showed moderate activity against A-549 cell lines. Conclusion:: Among the 5 indolyl pyrazole derivatives screened, compounds 4h and 4j showed significantly better activity with an IC50 of 33.12 and 34.24 μM, respectively. Further, structural tweaking of the synthesized new chemical entities may lead to potential hit/lead-like molecules.

Sign in / Sign up

Export Citation Format

Share Document