Functional Aspects of Ultra-rapid Heme Doming in Hemoglobin, Myoglobin, and the Myoglobin Mutant H93G

Franzen, Stefan; Bohn, B.; Poyart, Claire; DePillis, Gia D.; Boxer, Steven G.; Martin, Jean−Louis

doi:10.1074/jbc.270.4.1718

Cited by 36 publications

(47 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that the displacement of the iron out of the heme plane upon photodissociation occurs within a fraction of a picosecond (79,80). Under most circumstances this seemingly ballistic motion will precede any relaxation involving movements in the ␣ helices that have been triggered by the dissociation.…”

Section: Discussionmentioning

confidence: 99%

Spectroscopically and Kinetically Distinct Conformational Populations of Sol-Gel-encapsulated Carbonmonoxy Myoglobin

Samuni

Dantsker

Khan

et al. 2002

Journal of Biological Chemistry

108

View full text Add to dashboard Cite

We have used sol-gel encapsulation protocols to trap kinetically and spectroscopically distinct conformational populations of native horse carbonmonoxy myoglobin. The method allows for direct comparison of functional and spectroscopic properties of equilibrium and non-equilibrium populations under the same temperature and viscosity conditions. The results implicate tertiary structure changes that include the proximal heme environment in the mechanism for population-specific differences in the observed rebinding kinetics. Differences in the resonance Raman frequency of (Fe-His), the iron-proximal histidine stretching mode, are attributed to differences in the positioning of the F helix. For myoglobin, the degree of separation between the F helix and the heme is assigned as the conformational coordinate that modulates both this frequency and the innermost barrier controlling CO rebinding. A comparison with the behavior of encapsulated derivatives of human adult hemoglobin indicates that these CO binding-induced conformational changes are qualitatively similar to the tertiary changes that occur within both the R and T quaternary states. Protein-specific differences in the time scale for the proposed F helix relaxation are attributed to variations in the intra-helical hydrogen bonding patterns that help stabilize the position of the F helix. Myoglobin (Mb)1 continues to be used as a model protein system for investigations into how structure, dynamics, and reactivity interconnect to give rise to functionality. Recently there has been a renewed interest in myoglobin based on several new developments. From a functional point of view there are indications and suggestions that, apart from its physiological importance in facilitating oxygen diffusion, myoglobin has functions arising from its ability to participate in catalytic multisubstrate reactions involving such molecules as NO, O 2 , and H 2 O 2 (1-3). In addition the presence of apolar intra-protein substrate docking sites (the so-called Xe cavities) (4, 5) have recently been linked both to these newly proposed functions and to the kinetic patterns associated with geminate and bimolecular ligand binding (3, 6 -13).These new developments highlight fundamental biophysical issues that have not been fully addressed despite the extensive research effort that has been directed toward myoglobin. The issue that we address in this work relates to ligand reactivity as a function of conformation. Several studies show that myoglobin can adopt different tertiary conformations. In particular there is evidence that the equilibrium distribution of tertiary conformations is different for the deoxy (ferrous five coordinate) and CO derivatives of Mb. X-ray crystallographic studies show that there is a small clam shell-like rotation of the E and F helices in going from deoxy to COMb (14) as well as adjustments in the positioning of residues in the distal heme pocket (8 -10, 15, 16) that may or may not be related to the clam shell motion. Recent time-resolved x-ray crystallographic stud...

show abstract

Section: Discussionmentioning

confidence: 99%

Spectroscopically and Kinetically Distinct Conformational Populations of Sol-Gel-encapsulated Carbonmonoxy Myoglobin

Samuni

Dantsker

Khan

et al. 2002

Journal of Biological Chemistry

108

View full text Add to dashboard Cite

show abstract

“…However, despite the high spin configuration of iron, the doming for ferric species is expected to be smaller than ferrous myoglobins. 127 In fact, a minimisation including the Dom1 and Dom2 parameters (see the ESI † for a description of these parameters) yielded small values with large uncertainties (0.02 AE 0.06 for both parameters) and therefore we conclude that the heme is not domed. The pre-edge spectrum of metMb is shown in Fig.…”

Section: Metmbmentioning

confidence: 99%

Probing the electronic and geometric structure of ferric and ferrous myoglobins in physiological solutions by Fe K-edge absorption spectroscopy

Lima

Penfold

Veen

et al. 2014

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

We present an iron K-edge X-ray absorption study of carboxymyoglobin (MbCO), nitrosylmyoglobin (MbNO), oxymyoglobin (MbO 2 ), cyanomyoglobin (MbCN), aquomet myoglobin (metMb) and unligated myoglobin (deoxyMb) in physiological media. The analysis of the XANES region is performed using the full-multiple scattering formalism, implemented within the MXAN package. This reveals trends within the heme structure, absent from previous crystallographic and X-ray absorption analysis. In particular, the iron-nitrogen bond lengths in the porphyrin ring converge to a common value of about 2 Å, except for deoxyMb whose bigger value is due to the doming of the heme. The trends of the Fe-N e (His93) bond length is found to be consistent with the effect of ligand binding to the iron, with the exception of MbNO, which is explained in terms of the repulsive trans effect. We derive a high resolution description of the relative geometry of the ligands with respect to the heme and quantify the magnitude of the heme doming in the deoxyMb form. Finally, time-dependent density functional theory is used to simulate the pre-edge spectra and is found to be in good agreement with the experiment. The XAS spectra typically exhibit one pre-edge feature which arises from transitions into the unoccupied d s and d p À p ligand * orbitals. 1s -d p transitions contribute weakly for MbO 2 , metMb and deoxyMb.However, despite this strong Fe d contribution these transitions are found to be dominated by the dipole (1s -4p) moment due to the low symmetry of the heme environment.

show abstract

“…The H93G (ϩImd) mutant serves as a mimic of NT Mb in which the covalent bond between heme and globin is cleaved and an exogenous imidazole binds to iron freely in the proximal cavity (13). The sub-picosecond time-resolved RR spectra showed ultra-rapid heme doming following ligand dissociation in this cavity mutant, suggesting that the out-of-plane movement of iron is independent of its chemical linkage to His-93 in NT Mb (11). This left the question of whether this covalent bond is responsible for communication between the heme and the protein moiety.…”

Section: Conformational Changes In the N Terminus Upon Ligandmentioning

confidence: 99%

“…In addition, time-resolved resonance Raman (RR) measurements of the Fe-His stretching mode with visible laser pulses have demonstrated that, for Mb, the structural change takes place rapidly (time constant of ϳ120 ps) (10). However, the transmission of the heme structural change to globin via His-93 has become a matter of controversy because a fast structural change has also been observed for the Gly-93(ϩImd) mutant, which lacks the Fe-His covalent bond (11). Fig.…”

mentioning

confidence: 99%

Pathway of Information Transmission from Heme to Protein upon Ligand Binding/Dissociation in Myoglobin Revealed by UV Resonance Raman Spectroscopy

Gao

El-Mashtoly

Pal

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Gas sensory heme proteins respond to their environment by binding a specific gas molecule to heme and transmitting this primary binding signal to the protein. How the binding signal is transmitted from the heme to the protein remains to be clarified. Using UV resonance Raman (UVRR) spectroscopy, we investigated this pathway in sperm whale myoglobin as a model gas sensory heme protein. Based on the UVRR data and the effects of deleting one of three important pathways (His-93, 6-propionate, or 7-propionate), we determined the changes in the conformation of globin that occur upon binding of CO, nitric oxide (NO), or O 2 to heme and how they are transmitted from heme to globin. The UVRR results show that heme discriminates different ligands, resulting in different conformations in the globin protein. Specifically, NO induces changes in the spectrum of Trp residues in the A-helix that are significantly different from those induced by O 2 or CO binding. On the other hand, binding of O 2 to heme produces changes in the Tyr residues of the H-helix that are different from those induced by CO or NO binding. Furthermore, we found that cleavage of the FeHis-93 covalent bond eliminates communication to the terminal region of the H-helix and that the 7-propionate hydrogenbonding network is essential for transmitting the CO or NO binding signal to the N and C termini. Finally, the 6-propionate is important only for NO binding. Thus, the hydrogen-bonding network in the protein appears to be critical for intramolecular signal transduction in gas sensory heme proteins.The structural change in heme that occurs upon ligand binding/dissociation is the main process underlying the cooperativity in oxygen binding by Hb (1) and signal transduction by gas sensory heme proteins (2-4). This process is thought to mediate transmission of the heme ligand-binding signal to the hemebinding domain of the protein. Mb is a small heme-containing protein that can reversibly bind diatomic gaseous molecules (O 2 , NO, 2 and CO). Because Mb is well characterized, it is an ideal model for investigating the interactions between heme and protein moiety of gas sensory heme proteins. The deoxy form of Mb (deoxyMb) adopts a five-coordinate high spin structure with the iron atom 0.3 Å out of the heme plane, whereas the heme is planar in the ligated form (5-8). The outof-plane displacement of the iron atom is thought to be responsible for a conformational change between the deoxy and ligated forms of Mb.Our previous ultraviolet resonance Raman (UVRR) experiments, wherein Mb was excited at 244 nm, suggested that slight structural changes in Trp-7 and Tyr-151 occur upon CO binding (9). In addition, time-resolved resonance Raman (RR) measurements of the Fe-His stretching mode with visible laser pulses have demonstrated that, for Mb, the structural change takes place rapidly (time constant of ϳ120 ps) (10). However, the transmission of the heme structural change to globin via His-93 has become a matter of controversy because a fast structural change has also been ...

show abstract

Functional Aspects of Ultra-rapid Heme Doming in Hemoglobin, Myoglobin, and the Myoglobin Mutant H93G

Cited by 36 publications

References 20 publications

Spectroscopically and Kinetically Distinct Conformational Populations of Sol-Gel-encapsulated Carbonmonoxy Myoglobin

Spectroscopically and Kinetically Distinct Conformational Populations of Sol-Gel-encapsulated Carbonmonoxy Myoglobin

Probing the electronic and geometric structure of ferric and ferrous myoglobins in physiological solutions by Fe K-edge absorption spectroscopy

Pathway of Information Transmission from Heme to Protein upon Ligand Binding/Dissociation in Myoglobin Revealed by UV Resonance Raman Spectroscopy

Contact Info

Product

Resources

About