Human Hemoglobin
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2021 ◽  
Author(s):  
Joseph Clayton ◽  
Kat Ellis-Guardiola ◽  
Brandon Mahoney ◽  
Jess Soule ◽  
Robert T. Clubb ◽  
...  

Pathogenic Staphylococcus aureus actively acquires iron from human hemoglobin (Hb) using the IsdH surface receptor. Heme extraction is mediated by a tridomain unit within the receptor that contains its second (N2) and third (N3) NEAT domains joined by a helical linker domain. Extraction occurs within a dynamic complex, in which receptors engage each globin chain; the N2 domain tightly binds to Hb, while substantial inter-domain motions within the receptor enable its N3 domain to transiently distort the globin's heme pocket. Using molecular simulations, Markov modeling, and quantitative measurements of heme transfer kinetics, we show that directed inter-domain motions within the receptor play a critical role in the extraction process. The directionality of N3 domain motion and the rate of heme extraction is controlled by amino acids within a short, flexible inter-domain tether that connects the N2 and linker domains. In the wild-type receptor directed motions originating from the tether enable the N3 domain to populate configurations capable of distorting Hb's pocket, whereas mutant receptors containing altered tethers are less able to adopt these conformers and capture heme slowly via indirect processes in which Hb first releases heme into the solvent. Thus, our results show inter-domain motions within the IsdH receptor play a critical role in its ability to extract heme from Hb and highlight the importance of directed motions by the short, unstructured, amino acid sequence connecting the domains in controlling the directionality and magnitude of these functionally important motions.


2021 ◽  
Author(s):  
Julia Subbotina ◽  
Vladimir Lobaskin

Understanding the specifics of interaction between protein and nanomaterial is crucial for designing efficient, safe, and selective nanoplatforms, such as biosensor or nanocarrier systems. Routing experimental screening for the most suitable complementary pair of biomolecule and nanomaterial used in such nanoplatforms might be a resource-intensive task. While a variety of computational tools is available for pre-screening libraries of small drug molecules interacting with proteins, options for high-throughput screening of protein libraries for binding affinities to new and existing nanomaterials are limited. In the current work, we present the results of a systematic computational study of protein interaction with zero-valent silver nanoparticles using a multiscale approach. A variety of blood plasma and dietary proteins, namely, bovine and human serum albumins, bovine and human hemoglobin, papain, bromelain, lysozyme, and bovine lactoferrin, were examined. Selected combinations of nanomaterial and proteins can serve as a starting model for developing noble metal-based nanocarriers and biosensors. The computed binding (adsorption) characteristics for selected proteins were validated by experimental data reported in the literature. An advanced in silico nano-QSAR/QSPR interfacial descriptor 〖log⁡P〗^NM was also introduced to characterize the relative hydrophobicity/hydrophilicity of the nanomaterial.


Biochimie ◽  
2021 ◽  
Author(s):  
Zafar Rasheed ◽  
Adel Alharbi ◽  
Abdullah Alrakebeh ◽  
Khaled Almansour ◽  
Abdulaziz Almadi ◽  
...  

Author(s):  
Solmaz Hajizadeh ◽  
Karin Kettisen ◽  
Leif Bülow ◽  
Lei Ye

The production of a macroporous hydrogel column, known as cryogel, has been scaled up (up to 150 mL) in this work for the purification of human hemoglobin from non-clarified bacterial homogenates. Composite cryogels were synthesized in the presence of adult hemoglobin (HbA) to form a molecularly imprinted polymer (MIP)network where the affinity sites for the targeted molecule were placed directly on an acrylamide cryogel by protein imprinting during the cryogelation. The MIP composite cryogel column was first evaluated in a well-defined protein mixture. It showed high selectivity toward HbA in spite of the presence of serum albumin. Also, when examined in complex non-clarified E. coli cell homogenates, the column showed excellent chromatographic behavior. The binding capacity of a 50 mL column was thus found to be 0.88 and 1.2 mg/g, from a protein mixture and non-clarified cell homogenate suspension, respectively. The recovery and purification of the 50 mL column for separation of HbA from cell suspension were evaluated to be 79 and 58%, respectively. The MIP affinity cryogel also displayed binding and selectivity toward fetal Hb (HbF) under the same operational conditions.


2021 ◽  
Author(s):  
Joseph Jelinski ◽  
Madeline Cortez ◽  
Austen Terwilliger ◽  
Justin Clark ◽  
Anthony Maresso

Anthrax disease is caused by infection with the bacteria Bacillus anthracis which, if left untreated, can result in fatal bacteremia and toxemia. Current treatment for infection requires prolonged administration of antibiotics. Despite this, inhalational and gastrointestinal anthrax still result in lethal disease. By identifying key metabolic steps that B. anthracis uses to grow in host-like environments, new targets for antibacterial strategies can be identified. Here, we report that the ilvD gene, which encodes dihydroxyacid dehydratase in the putative pathway for synthesizing branched chain amino acids, is necessary for B. anthracis to synthesize isoleucine de novo in an otherwise limiting microenvironment. We observed that Δ ilvD B. anthracis cannot grow in media lacking isoleucine, but growth is restored when exogenous isoleucine is added. In addition, ΔilvD bacilli are unable to utilize human hemoglobin or serum albumin to overcome isoleucine auxotrophy, but can when provided with the murine forms. This species-specific effect is due to the lack of isoleucine in human hemoglobin. Furthermore, even when supplemented with physiological levels of human serum albumin, apotransferrin, fibrinogen, and IgG, the ilvD knockout strain grew poorly relative to non-supplemented wild-type. In addition, comparisons upon infecting humanized mice suggest that murine hemoglobin is a key source of isoleucine for both WT and Δ ilvD bacilli. Further growth comparisons in murine and human blood show that the auxotrophy is detrimental for growth in human blood, not murine. This report identifies ilvD as necessary for isoleucine production in B. anthracis , and that it plays a key role in allowing the bacilli to effectively grow in isoleucine poor hosts. Importance Anthrax disease, caused by B. anthracis , can cause lethal bacteremia and toxemia, even following treatment with antibiotics. This report identifies the ilvD gene, which encodes a dihydroxyacid dehydratase, as necessary for B. anthracis to synthesize the amino acid isoleucine in a nutrient-limiting environment, such as its mammalian host. The use of this strain further demonstrated a unique species-dependent utilization of hemoglobin as an exogenous source of extracellular isoleucine. By identifying mechanisms that B. anthracis uses to grow in host-like environments, new targets for therapeutic intervention are revealed.


2021 ◽  
Author(s):  
Negar Hajimohammadi Oushani ◽  
Masoumeh Valipour ◽  
Parvaneh Maghami

Abstract BackgroundVinyl chloride (VC) a colorless gas with a pleasant odor that is capable of entering the body through oral or inhalation routes. Extensive studies on this compound indicated that it is a carcinogen, and Vinyl chloride exposure can result in a specific type of cancer in VC workers. Whereas hemoglobin plays a vital role in oxygen transfer throughout the body, the effect of VC on human hemoglobin has not been studied in a molecular aspect. Furthermore, selenium as an antioxidant is a vital factor for the health of humans and animals. Therefore, the effect of the antioxidant capability of selenium on the interaction between vinyl chloride and hemoglobin was studied.MethodsThe effect of the antioxidant capability of selenium on the interaction between VC and hemoglobin was investigated by different spectroscopy methods such as UV-visible, Fourier-transform infrared, chemiluminescence, and fluorescence spectroscopies and molecular dockingResultsThe results indicated the destruction of hemoglobin structure in the presence of different concentrations of vinyl chloride, but in the presence of selenium, the damaging effect of VC on hemoglobin structure was decreased, relying on its antioxidant capability results.ConclusionsAccording to our findings, vinyl chloride destroyed hemoglobin structure utilizing ROS production, and the presence of selenium as an antioxidant inhibits the destroying effect of vinyl chloride on hemoglobin


2021 ◽  
Author(s):  
C. Philip Larson

The Solubility of Halothane in Blood and Tissue Homogenates. By Larson CP, Eger EI, Severinghaus JW. Anesthesiology 1962; 23:349–55. Measured samples of human and bovine blood, human hemoglobin, and tissue homogenates from human fat and both human and bovine liver, kidney, muscle, whole brain, and separated gray and white cortex were added to stoppered 2,000-ml Erlenmeyer flasks. To each flask, 0.1 ml of liquid halothane was added under negative pressure using a calibrated micropipette. After the flask was agitated for 2 to 4 h to achieve equilibrium between the gas and blood or tissue contents, a calibrated infrared halothane analyzer was used to measure the concentration of halothane vapor. Calculated partition coefficients ranged from 0.7 for water to 2.3 for blood and from 3.5 for human or bovine kidney to 6 for human whole brain or liver and 8 for human muscle. Human peritoneal fat had a value of 138. The human blood–gas partition coefficient of 2.3 as determined by this equilibration method was well below the previously published value of 3.6.


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