Correction: the five-to-six-coordination transition of ferric human serum heme-albumin is allosterically-modulated by ibuprofen and warfarin: a combined XAS and MD study.
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ABSTRACT:
SUBMITTER: PLOS ONE Staff
PROVIDER: S-EPMC4380330 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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Correction: the five-to-six-coordination transition of ferric human serum heme-albumin is allosterically-modulated by ibuprofen and warfarin: a combined XAS and MD study.
PloS one 20150331 3
[This corrects the article DOI: 10.1371/journal.pone.0104231.]. ...[more]
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Project description:Human serum albumin (HSA) is involved physiologically in heme scavenging; in turn, heme-albumin (HSA-heme-Fe) displays globin-like properties. Here, the allosteric effect of ibuprofen and warfarin on the local atomic structure around the ferric heme-Fe (heme-Fe(III)) atom of HSA-heme-Fe (HSA-heme-Fe(III)) has been probed by Fe-K edge X-ray absorption spectroscopy (XAS). The quantitative analysis of the Fe-K edge extended X-ray absorption fine structure (EXAFS) signals and modeling of the near edge (XANES) spectral features demonstrated that warfarin and ibuprofen binding modify the local structure of the heme-Fe(III). Combined XAS data analysis and targeted molecular dynamics (MD) simulations provided atomic resolution insights of protein structural rearrangements required to accommodate the heme-Fe(III) upon ibuprofen and warfarin binding. In the absence of drugs, the heme-Fe(III) atom is penta-coordinated having distorted 4+1 configuration made by the nitrogen atoms of the porphyrin ring and the oxygen phenoxy atom of the Tyr161 residue. MD simulations show that ibuprofen and warfarin association to the secondary fatty acid (FA) binding site 2 (FA2) induces a reorientation of domain I of HSA-heme-Fe(III), this leads to the redirection of the His146 residue providing an additional bond to the heme-Fe(III) atom, providing the 5+1 configuration. The comparison of Fe-K edge XANES spectra calculated using MD structures with those obtained experimentally confirms the reliability of the proposed structural model. As a whole, combining XAS and MD simulations it has been possible to provide a reliable model of the heme-Fe(III) atom coordination state and to understand the complex allosteric transition occurring in HSA-heme-Fe(III) upon ibuprofen and warfarin binding.
| S-EPMC4143227 | biostudies-literature
Project description:Human serum albumin (HSA) participates in heme scavenging; in turn, heme endows HSA with myoglobin-like reactivity and spectroscopic properties. Here, the allosteric effect of ibuprofen on peroxynitrite isomerization to NO(3)(-) catalyzed by ferric human serum heme-albumin (HSA-heme-Fe(III)) is reported. Data were obtained at 22.0 degrees C. HSA-heme-Fe(III) catalyzes peroxynitrite isomerization in the absence and presence of CO(2); the values of the second order catalytic rate constant (k(on)) are 4.1 x 10(5) and 4.5 x 10(5) m(-1) s(-1), respectively. Moreover, HSA-heme-Fe(III) prevents peroxynitrite-mediated nitration of free added l-tyrosine. The pH dependence of k(on) (pK(a) = 6.9) suggests that peroxynitrous acid reacts preferentially with the heme-Fe(III) atom, in the absence and presence of CO(2). The HSA-heme-Fe(III)-catalyzed isomerization of peroxynitrite has been ascribed to the reactive pentacoordinated heme-Fe(III) atom. In the absence and presence of CO(2), ibuprofen impairs dose-dependently peroxynitrite isomerization by HSA-heme-Fe(III) and facilitates the nitration of free added l-tyrosine; the value of the dissociation equilibrium constant for ibuprofen binding to HSA-heme-Fe(III) (L) ranges between 7.7 x 10(-4) and 9.7 x 10(-4) m. Under conditions where [ibuprofen] is >>L, the kinetics of HSA-heme-Fe(III)-catalyzed isomerization of peroxynitrite is superimposable to that obtained in the absence of HSA-heme-Fe(III) or in the presence of non-catalytic HSA-heme-Fe(III)-cyanide complex and HSA. Ibuprofen binding impairs allosterically peroxynitrite isomerization by HSA-heme-Fe(III), inducing the hexacoordination of the heme-Fe(III) atom. These results represent the first evidence for peroxynitrite isomerization by HSA-heme-Fe(III), highlighting the allosteric modulation of HSA-heme-Fe(III) reactivity by heterotropic interaction(s), and outlining the role of drugs in modulating HSA functions. The present results could be relevant for the drug-dependent protective role of HSA-heme-Fe(III) in vivo.
| S-EPMC2781501 | biostudies-literature
Project description:The solvation shell structures of Ca2+ in aqueous and organic solutions probed by calcium L-edge soft X-ray absorption spectroscopy (XAS) and DFT/MD simulations show the coordination number of Ca2+ to be negatively correlated with the electrolyte concentration and the steric hindrance of the solvent molecule. In this work, the calcium L-edge soft XAS demonstrates its sensitivity to the surrounding chemical environment. Additionally, the total electron yield (TEY) mode is surface sensitive because the electron penetration depth is limited to a few nanometers. Thus this study shows its implications for future battery studies, especially for probing the electrolyte/electrode interface for electrochemical reactions under in situ/operando conditions.
| S-EPMC9055519 | biostudies-literature
Project description:Human serum albumin (HSA), the most abundant protein in human plasma, could be considered as a prototypic monomeric allosteric protein, since the ligand-dependent conformational adaptability of HSA spreads beyond the immediate proximity of the binding site(s). As a matter of fact, HSA is a major transport protein in the bloodstream and the regulation of the functional allosteric interrelationships between the different binding sites represents a fundamental information for the knowledge of its transport function. Here, kinetics and thermodynamics of the allosteric modulation: (i) of carbon monoxide (CO) binding to ferrous human serum heme-albumin (HSA-heme-Fe(II)) by warfarin (WF), and (ii) of WF binding to HSA-heme-Fe(II) by CO are reported. All data were obtained at pH 7.0 and 25°C. Kinetics of CO and WF binding to the FA1 and FA7 sites of HSA-heme-Fe(II), respectively, follows a multi-exponential behavior (with the same relative percentage for the two ligands). This can be accounted for by the existence of multiple conformations and/or heme-protein axial coordination forms of HSA-heme-Fe(II). The HSA-heme-Fe(II) populations have been characterized by resonance Raman spectroscopy, indicating the coexistence of different species characterized by four-, five- and six-coordination of the heme-Fe atom. As a whole, these results suggest that: (i) upon CO binding a conformational change of HSA-heme-Fe(II) takes place (likely reflecting the displacement of an endogenous ligand by CO), and (ii) CO and/or WF binding brings about a ligand-dependent variation of the HSA-heme-Fe(II) population distribution of the various coordinating species. The detailed thermodynamic and kinetic analysis here reported allows a quantitative description of the mutual allosteric effect of CO and WF binding to HSA-heme-Fe(II).
| S-EPMC3605432 | biostudies-literature
Project description:X-ray absorption near-edge structure (XANES) spectra of ferric myoglobin from horse heart have been acquired as a function of pH (between 5.3 and 11.3). At pH = 11.3 temperature-dependent spectra (between 20 and 293 K) have been collected as well. Experimental data solve three main conformations of the Fe-heme: the first, at low pH, is related to high-spin aquomet-myoglobin (Mb+OH2). The other two, at pH 11.3, are related to hydroxymet-myoglobin (Mb+OH-), and are in thermal equilibrium, corresponding to high- and low-spin Mb+OH-. The structure of the three Fe-heme conformations has been assigned according to spin-resolved multiple scattering simulations and fitting of the XANES data. The chemical transition between Mb+OH2 and high-spin Mb+OH-, and the spin transition of Mb+OH-, are accompanied by changes of the Fe coordination sphere due to its movement toward the heme plane, coupled to an increase of the axial asymmetry.
| S-EPMC1299987 | biostudies-other
Project description:A new end-on low-spin ferric heme peroxide, [(PIm )FeIII -(O2 2- )]- (PIm -P), and subsequently formed hydroperoxide species, [(PIm )FeIII -(OOH)] (PIm -HP) are generated utilizing the iron-porphyrinate PIm with its tethered axial base imidazolyl group. Measured thermodynamic parameters, the ferric heme superoxide [(PIm )FeIII -(O2 ⋅- )] (PIm -S) reduction potential (E°') and the PIm -HP pKa value, lead to the finding of the OO-H bond-dissociation free energy (BDFE) of PIm -HP as 69.5 kcal mol-1 using a thermodynamic square scheme and Bordwell relationship. The results are validated by the observed oxidizing ability of PIm -S via hydrogen-atom transfer (HAT) compared to that of the F8 superoxide complex, [(F8 )FeIII -(O2 .- )] (S) (F8 =tetrakis(2,6-difluorophenyl)porphyrinate, without an internally appended axial base imidazolyl), as determined from reactivity comparison of superoxide complexes PIm -S and S with the hydroxylamine (O-H) substrates TEMPO-H and ABNO-H.
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Project description:The interaction of three free-base meso-tris(p-X-phenyl)corroles H3[TpXPC] (X = H, CH3, OCH3) with Re2(CO)10 at 235 °C in the presence of K2CO3 in o-dichlorobenzene has led to putative rhenium biscorrole sandwich compounds with the formula ReH[TpXPC]2. Density functional theory calculations and Re L3-edge extended X-ray absorption fine structure measurements suggest a seven-coordinate metal center, with the "extra" hydrogen located on one of the corrole nitrogens. The complexes can be deprotonated by a base such as 1,8-diazabicyclo[5.4.0]undec-7-ene, resulting in a substantial sharpening of the UV-vis spectra and split Soret bands, consistent with the generation of C2-symmetric anions. Both the seven-coordinate neutral and eight-coordinate anionic forms of the complexes represent a new coordination motif in the field of rhenium-porphyrinoid interactions.
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Project description:Heme can serve as iron source in many environments, including the iron-poor animal host environment. The fungal pathobiont Candida albicans expresses a family of extracellular CFEM hemophores that capture heme from host proteins and transfer it across the cell wall to the cell membrane, to be endocytosed and utilized as heme or iron source. Here, we identified Frp1 and Frp2, two ferric reductase (FRE)-related proteins that lack an extracellular N-terminal substrate-binding domain, as being required for hemoglobin heme utilization and for sensitivity to toxic heme analogs. Frp1 and Frp2 redistribute to the plasma membrane in the presence of hemin, consistent with a direct role in heme trafficking. Expression of Frp1 with the CFEM hemophore Pga7 can promote heme utilization in Saccharomyces cerevisiae as well, confirming the functional interaction between these proteins. Sequence and structure comparison reveals that the CFEM hemophores are related to the FRE substrate-binding domain that is missing in Frp1/2. We conclude that Frp1/2 and the CFEM hemophores form a functional complex that evolved from FREs to enable extracellular heme uptake.
| S-EPMC9635878 | biostudies-literature
Project description:Many HNO-scavenging pathways exist to regulate its biological and pharmacological activities. Such reactions often involve ferric heme proteins and form an important basis for HNO probe development. However, mechanisms of HNO reactions with ferric heme proteins are largely unknown. We performed a computational investigation using metmyoglobin and catalase as representative ferric heme proteins with neutral and negatively charged axial ligands to provide the first detailed pathways. The results reproduced experimental barriers well with an average error of 0.11 kcal mol-1 . The rate-limiting step was found to be dissociation of the resting ligand or HNO coordination when there is no resting ligand. For both heme proteins, in contrast to the non-heme case, the reductive nitrosylation step was found to be barrierless proton-coupled electron transfer, which provides the major thermodynamic driving force for the overall reaction. The origin of the difference in reactivity between metmyoglobin and catalase was also revealed.
| S-EPMC6522253 | biostudies-literature
Project description:Human serum albumin (HSA) acts as a carrier for testosterone, other sex hormones, fatty acids, and drugs. However, the dynamics of testosterone's binding to HSA and the structure of its binding sites remain incompletely understood. Here, we characterize the dynamics of testosterone's binding to HSA and the stoichiometry and structural location of the binding sites using 2-dimensional nuclear magnetic resonance (2D NMR), fluorescence spectroscopy, 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid dipotassium salt partitioning, and equilibrium dialysis, complemented by molecular modeling. 2D NMR studies showed that testosterone competitively displaced 18-[13C]-oleic acid from at least 3 known fatty acid binding sites on HSA that also bind many drugs. Binding isotherms of testosterone's binding to HSA generated using fluorescence spectroscopy and equilibrium dialysis were nonlinear and the apparent dissociation constant varied with different concentrations of testosterone and HSA. The binding isotherms neither conformed to a linear binding model with 1:1 stoichiometry nor to 2 independent binding sites; the binding isotherms were most consistent with 2 or more allosterically coupled binding sites. Molecular dynamics studies revealed that testosterone's binding to fatty acid binding site 3 on HSA was associated with conformational changes at site 6, indicating that residues in in these 2 distinct binding sites are allosterically coupled. There are multiple, allosterically coupled binding sites for testosterone on HSA. Testosterone shares these binding sites on HSA with free fatty acids, which could displace testosterone from HSA under various physiological states or disease conditions, affecting its bioavailability.
| S-EPMC7774055 | biostudies-literature