The porphyrin-iron hybrid hemoglobins. Absence of the Fe-His bonds in one type of subunits favors a deoxy-like structure with low oxygen affinity

Fujii, M; Hori, Hiroshi; Miyazaki, Gentaro; Morimoto, Hideki; Yonetani, Takashi

doi:10.1016/s0021-9258(18)82269-4

Cited by 40 publications

(18 citation statements)

References 54 publications

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“…This shift is due to the proximal imidazole adopting a less tilted geometry since the repulsive interactions between the pyrrole nitrogens and imidazole carbons increase with decreasing iron displacement (Rousseau & Friedman, 1988;Friedman, 1994). According to Yonetani and coworkers, decoupling the F helix from the heme through either bond rupture or removal of the iron should allow the F helix to shift even further toward the EF corner (Fujii et al, 1993). Thus, these T state "forces" can be present to varying degrees based on solution conditions and the presence of mutations, effectors, and ligands to produce a distribution of both T state tertiary conformations and ligand binding properties.…”

Section: Discussionmentioning

confidence: 99%

A Possible Allosteric Communication Pathway Identified through a Resonance Raman Study of Four β37 Mutants of Human Hemoglobin A

Peterson

Friedman

1998

Biochemistry

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The highly conserved tryptophan at position beta37 occupies a key locus at the hinge region within the alpha1beta2 interface of the mammalian hemoglobins. This residue is thought to play an important role in mediating the heme-heme interaction associated with the cooperative binding of oxygen; however, its explicit function is unclear. In this study, the proximal heme environments of several beta37 mutants of adult human hemoglobin (HbA) are probed using visible (Soret band enhanced) resonance Raman spectroscopy. In the equilibrium deoxy derivatives of these mutants, a systematic variation in proximal strain, as reflected in the iron-proximal histidine (F8) stretching frequency, nu(Fe-His), is seen upon mutation of the beta37 residue. The variation in proximal strain correlates with both the ligand binding rates [Kwiatkowski et al. (1998) Biochemistry 37, 4325-4335] and conformational changes observed at the FG corner through X-ray crystallography [Kavanaugh et al. (1998) Biochemistry 37, 4358-4373]. The results from the deoxy samples indicate a plasticity of the tertiary structure within the T quaternary state. The correlation between the X-ray data and the Raman supports the idea that the proximal strain at the heme within the T state can be modulated by a combination of forces including those arising from the hinge region of the alpha1beta2 interface, from the binding of allosteric effectors, and from the degree of iron displacement from the heme plane. Each of these contributors appears to operate through a shifting of the F helix either away from or toward the FG corner. The Raman spectra obtained from the 10 ns CO photoproduct of the beta37 mutant Hb's indicate that these mutants contain an altered coupling between the R state alpha1beta2 interface and the proximal heme environment. This altered coupling could be due to either dissociation of the ligated mutant tetramers into dimers or the formation of an R state tetramer with significantly weakened hydrogen bonds and van der Waals contacts between the alpha1 and beta2 subunits at the interface. In either case, the results reveal a clear-cut structural basis for the quaternary enhancement effect in which the normal R state quaternary structure produces a higher affinity ligand binding site than that which occurs in the corresponding dimeric form of the protein. The normal R state interface is shown to be important for stabilizing a favorable ligand binding environment that persists long enough after laser photolysis to enhance the geminate rebinding process within the photoproduct. The addition of IHP to the solution of mutant COHb proteins results in photoproduct spectra that are all identical and are consistent with the ligand-bound derivatives having either a T state structure or a very strained and anomalous R state structure.

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Section: Discussionmentioning

confidence: 99%

A Possible Allosteric Communication Pathway Identified through a Resonance Raman Study of Four β37 Mutants of Human Hemoglobin A

Peterson

Friedman

1998

Biochemistry

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“…In this case, Tyr-R42 and Tyr-β145 must be influenced by the passageway originating from the R subunits. On the other hand, R(porphyrin) 2 β(Fe) 2 Hb is regarded as the T-(low affinity extreme) state at low pH regardless of the ligation at the β subunits because of the absence of the Fe-His bond of R heme (42). The UVRR spectrum of R(porphyrin) 2 β(Fe) 2 Hb, which has not yet been obtained, would be close to that of R NO β deoxy at pH 5.5 in the presence of IHP observed in this study.…”

Section: Discussionmentioning

confidence: 99%

UV Resonance Raman Studies of α-Nitrosyl Hemoglobin Derivatives: Relation between the α1−β2 Subunit Interface Interactions and the Fe−Histidine Bonding of α Heme

et al. 1999

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Human alpha-nitrosyl beta-deoxy hemoglobin A, alpha(NO)beta(deoxy), is considered to have a T (tense) structure with the low O(2) affinity extreme and the Fe-histidine (His87) (Fe-His) bond of alpha heme cleaved. The Fe-His bonding of alpha heme and the intersubunit interactions at the alpha 1-beta 2 contact of alpha(NO)-Hbs have been examined under various conditions with EPR and UV resonance Raman (UVRR) spectra excited at 235 nm, respectively. NOHb at pH 6.7 gave the UVRR spectrum of the R structure, but in the presence of inositol-hexakis-phosphate (IHP) for which the Fe-His bond of the alpha heme is broken, UVRR bands of Trp residues behaved half-T-like while Tyr bands remained R-like. The half-ligated nitrosylHb, alpha(NO)beta(deoxy), in the presence of IHP at pH 5.6, gave T-like UVRR spectra for both Tyr and Trp, but binding of CO to its beta heme (alpha(NO)beta(CO)) changed the UVRR spectrum to half-T-like. Binding of NO to its beta heme (NOHb) changed the UVRR spectrum to 70% T-type for Trp but almost R-type for Tyr. When the pH was raised to 8.2 in the presence of IHP, the UVRR spectrum of NOHb was the same as that of COHb. EPR spectra of these Hbs indicated that the Fe-His bond of alpha(NO) heme is partially cleaved. On the other hand, the UVRR spectra of alpha(NO)beta(deoxy) in the absence of IHP at pH 8.8 showed the T-like UVRR spectrum, but the EPR spectrum indicated that 40-50% of the Fe-His bond of alpha hemes was intact. Therefore, it became evident that there is a qualitative correlation between the cleavage of the Fe-His bond of alpha heme and T-like contact of Trp-beta 37. We note that the behaviors of Tyr and Trp residues at the alpha 1-beta 2 interface are not synchronous. It is likely that the behaviors of Tyr residues are controlled by the ligation of beta heme through His-beta 92(F8)-->Val-beta 98(FG5)-->Asp-beta 99(G1 )-->Tyr-alpha 42(C7) or Tyr-beta 145(HC2).

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“…In addition and of specific interest for this study are the Fe-Co hybrids (11)(12)(13). For the unliganded Co porphyrin the metal ion does not lie as far out of the plane of the porphyrin as in deoxyheme or Zn porphyrin, and the Co-proximal histidine bond length is less than that of the Fe(II)-histidine bond (14). As a result the heme-F helix separation for subunits with five-coordinate Co-substituted heme is intermediate between the maximally separated position for five-coordinate Fe(II) or Zn hemes and the minimally separated position for either CO heme, Cr(III) porphyrin or Mn(III) porphyrin.…”

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confidence: 99%

Functional and Spectroscopic Characterization of Half-Liganded Iron−Zinc Hybrid Hemoglobin: Evidence for Conformational Plasticity within the T State^,

et al. 2003

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Functionally distinct conformations of HbA (human adult hemoglobin) were probed using deoxy and diliganded derivatives of symmetric Fe-Zn hybrids of HbA. To expand the range of accessible structures, different environments were utilized including solution, sol-gel encapsulation, and crystals. Further structural and functional modulation was achieved by the addition of allosteric effectors. Functional characterization included oxygen affinity measurements, CO combination rates, and geminate and bimolecular CO recombination, after photodissociation. The conformational properties were studied using visible resonance Raman spectroscopy as a probe of local tertiary structure at the iron-containing hemes and UV resonance Raman spectroscopy as a probe of elements of the globin known to be sensitive to quaternary structure. The combined results show a pattern in which there is a progression of conformational and functional properties that are consistent with a picture in which the T quaternary structure can accommodate a range of tertiary conformations (plasticity). At one end of the distribution is the equilibrium deoxy T state conformation that has the lowest ligand reactivity. At the other end of the distribution are T state conformations with higher ligand reactivity that exhibit "loosened" T state constraints within the globin including the alpha(1)beta(2) interface and reduced proximal strain at the heme.

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The porphyrin-iron hybrid hemoglobins. Absence of the Fe-His bonds in one type of subunits favors a deoxy-like structure with low oxygen affinity

Cited by 40 publications

References 54 publications

A Possible Allosteric Communication Pathway Identified through a Resonance Raman Study of Four β37 Mutants of Human Hemoglobin A

A Possible Allosteric Communication Pathway Identified through a Resonance Raman Study of Four β37 Mutants of Human Hemoglobin A

UV Resonance Raman Studies of α-Nitrosyl Hemoglobin Derivatives: Relation between the α1−β2 Subunit Interface Interactions and the Fe−Histidine Bonding of α Heme

Functional and Spectroscopic Characterization of Half-Liganded Iron−Zinc Hybrid Hemoglobin: Evidence for Conformational Plasticity within the T State^,

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The porphyrin-iron hybrid hemoglobins. Absence of the Fe-His bonds in one type of subunits favors a deoxy-like structure with low oxygen affinity

Cited by 40 publications

References 54 publications

A Possible Allosteric Communication Pathway Identified through a Resonance Raman Study of Four β37 Mutants of Human Hemoglobin A

A Possible Allosteric Communication Pathway Identified through a Resonance Raman Study of Four β37 Mutants of Human Hemoglobin A

UV Resonance Raman Studies of α-Nitrosyl Hemoglobin Derivatives: Relation between the α1−β2 Subunit Interface Interactions and the Fe−Histidine Bonding of α Heme

Functional and Spectroscopic Characterization of Half-Liganded Iron−Zinc Hybrid Hemoglobin: Evidence for Conformational Plasticity within the T State,

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Functional and Spectroscopic Characterization of Half-Liganded Iron−Zinc Hybrid Hemoglobin: Evidence for Conformational Plasticity within the T State^,