Molecular oxygen binding with α and β subunits within the R quaternary state of human hemoglobin in solutions and porous sol–gel matrices

Lepeshkevich, S. V.; Parkhats, Marina V.; Stepuro, I. I.; Джагаров, Б. М.

doi:10.1016/j.bbapap.2009.08.019

Cited by 17 publications

(18 citation statements)

References 35 publications

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“…Approximately half the persisting population rebinds in a delayed geminate phase with a time constant averaging 33.5 ± 2 ns (~30 μs −1 ) over a range of pH spanning 6.1 to 8.5 [37]. Our 4-state model provides a framework for assigning these rates to specific processes in specific subunits.…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, in the limit ϕ B = 1.0, the escaped fraction sums to a maximum of ~2% of the total photolyzed population. Since this amplitude is small compared to the 26% amplitude for the persisting deoxy population [37], the delayed geminate rebinding phase necessarily involves ligands that bypassed the B sites during photolysis, i.e., ϕ B is less than 1.0. Since the α subunit accounts for half of all hemes, and therefore half of the photolyzed O 2 , its 49% geminate amplitude implies that 98% of the O 2 in the α subunit rebinds from its B site.…”

Section: Resultsmentioning

confidence: 99%

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Real-time tracking of CO migration and binding in the α and β subunits of human hemoglobin via 150-ps time-resolved Laue crystallography

et al. 2013

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We have developed the method of picosecond Laue crystallography and used this capability to probe ligand dynamics in tetrameric R-state hemoglobin (Hb). Time-resolved, 2 Å-resolution electron density maps of photolyzed HbCO reveal the time-dependent population of CO in the binding (A) and primary docking (B) sites of both α and β subunits from 100 ps to 10 μs. The proximity of the B site in the β subunit is about 0.25 Å closer to its A binding site, and its kBA rebinding rate (~300 μs−1) is six times faster, suggesting distal control of the rebinding dynamics. Geminate rebinding in the β subunit exhibits both prompt and delayed geminate phases. We developed a microscopic model to quantitatively explain the observed kinetics, with three states for the α subunit and four states for the β subunit. This model provides a consistent framework for interpreting rebinding kinetics reported in prior studies of both HbCO and HbO2.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Real-time tracking of CO migration and binding in the α and β subunits of human hemoglobin via 150-ps time-resolved Laue crystallography

et al. 2013

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“…Interestingly, the dynamics of chain β significantly exceeds that of chain α in all the cases. Previous laser flash photolysis experiments reported the capability of the β subunit, with respect to the α one, to faster release small ligands 45,46 , with a possible implication of a different intrinsic dynamics. Furthermore, the diverse flexibility of α and β chains is also reflected in very different rates of spontaneous heme release from Hb, with β of spontaneous heme release from Hb, with β chains releasing it about 50-fold fastere than α chains.…”

Section: Discussionmentioning

confidence: 99%

Interaction of human hemoglobin and semi-hemoglobins with the Staphylococcus aureus hemophore IsdB: a kinetic and mechanistic insight

Gianquinto

Moscetti

Bei

et al. 2019

Sci Rep

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Among multidrug-resistant bacteria, methicillin-resistant Staphylococcus aureus is emerging as one of the most threatening pathogens. S. aureus exploits different mechanisms for its iron supply, but the preferred one is acquisition of organic iron through the expression of hemoglobin (Hb) receptors. One of these, IsdB, belonging to the Isd (Iron-Regulated Surface Determinant) system, was shown to be essential for bacterial growth and virulence. Therefore, interaction of IsdB with Hb represents a promising target for the rational design of a new class of antibacterial molecules. However, despite recent investigations, many structural and mechanistic details of complex formation and heme extraction process are still elusive. By combining site-directed mutagenesis, absorption spectroscopy, surface plasmon resonance and molecular dynamics simulations, we tackled most of the so far unanswered questions: (i) the exact complex stoichiometry, (ii) the microscopic kinetic rates of complex formation, (iii) the IsdB selectivity for binding to, and extracting heme from, α and β subunits of Hb, iv) the role of specific amino acid residues and structural regions in driving complex formation and heme transfer, and (v) the structural/dynamic effect played by the hemophore on Hb. The ability of bacterial pathogens to establish infections relies on the adaptation of bacterial metabolism to the environment found within the host, which is often severely nutrient-restricted and a site for competition with commensal microorganisms and other pathogens 1,2. A well-characterized mechanism of adaptation to the nutritional environment of the host is represented by the expression of redundant iron-acquisition systems, both in Gram + and Grambacteria, to provide iron supply to support invasion and proliferation 3. Iron is an essential nutrient for both the pathogen and the host, but also a toxic element due to its involvement in Fenton chemistry and Haber-Weiss reactions that generate reactive oxygen species (ROS) 4. For this reason, vertebrates have put in place strategies to maintain very low concentrations of free iron in body fluids (down to 10 −18-10 −24 M) 4,5 achieving two goals, the first being limiting toxicity and the second creating an iron-restricted environment for pathogens 6,7. In S. aureus, iron scavenging is achieved by at least three different mechanisms: i) acquisition of inorganic iron through production of siderophores, ii) expression of hemoglobin (Hb) receptors, and iii) acquisition of inorganic iron through transporters 4. Heme is the preferred iron source during the initial phase of infection 8

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“…4C-7C and ESI Fig. S2C † 43 for native oxyhemoglobin 22 as well as for the a and b subunits within native oxyhemoglobin, 22 are summarized for comparison. As it is seen from Table 1, the values of F 3 , evaluated in the present work for the isolated a SH and b SH chains as well as for the native oxyhemoglobin, are in a good agreement with the corresponding values of d escape determined previously.…”

Section: Molecular Oxygen Rebindingmentioning

confidence: 99%

“…20 A complete kinetic description of the O 2 rebinding with triliganded R-state Hb at room temperature has been presented. 21,22 These studies reported triple-exponential geminate O 2 rebinding in which photolyzed population rebinds via two prompt geminate phases with 0.14 and 1 ns time constants, and via another delayed geminate phase with a $30 ns time constant. Assigning all these geminate phases to specic processes in specic subunits is a very difficult task.…”

Section: Introductionmentioning

confidence: 99%

Towards understanding non-equivalence of α and β subunits within human hemoglobin in conformational relaxation and molecular oxygen rebinding

et al. 2021

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Molecular oxygen binding with α and β subunits within the R quaternary state of human hemoglobin in solutions and porous sol–gel matrices

Cited by 17 publications

References 35 publications

Real-time tracking of CO migration and binding in the α and β subunits of human hemoglobin via 150-ps time-resolved Laue crystallography

Real-time tracking of CO migration and binding in the α and β subunits of human hemoglobin via 150-ps time-resolved Laue crystallography

Interaction of human hemoglobin and semi-hemoglobins with the Staphylococcus aureus hemophore IsdB: a kinetic and mechanistic insight

Towards understanding non-equivalence of α and β subunits within human hemoglobin in conformational relaxation and molecular oxygen rebinding

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