New Light on Allostery:  Dynamic Resonance Raman Spectroscopy of Hemoglobin Kempsey

Hu, Xuehua; Rodgers, Kenton R.; Mukerji, Ishita; Spiro, Thomas G.

doi:10.1021/bi982513c

Cited by 42 publications

(77 citation statements)

References 35 publications

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“…44 -49 The previous working model involved breaking and reforming of tertiary H-bonds in response to deligation, followed by formation of the T-state quaternary contacts. 18,24 This picture is supported by the present results, but the quaternary contacts are found not to form simultaneously. Rather, the "hinge" contacts in the critical a 1 b 2 interface 30 form significantly earlier than do the "switch" contacts.…”

Section: Introductionsupporting

confidence: 86%

Time-resolved Absorption and UV Resonance Raman Spectra Reveal Stepwise Formation of T Quaternary Contacts in the Allosteric Pathway of Hemoglobin

Balakrishnan

Case

Pevsner

et al. 2004

Journal of Molecular Biology

158

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Section: Introductionsupporting

confidence: 86%

Time-resolved Absorption and UV Resonance Raman Spectra Reveal Stepwise Formation of T Quaternary Contacts in the Allosteric Pathway of Hemoglobin

Balakrishnan

Case

Pevsner

et al. 2004

Journal of Molecular Biology

158

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“…A likely explanation is that for hemoglobin there is an extensive series of hydrogen bonds and salt bridges functioning as scaffolding that maintains the spacing between pairs of ␣ helices (71,98,108,109). By damping rapid change in inter-helical spacing, the scaffolding will slow the response time of the E-F helices to the sudden local changes associated with ligand dissociation/association.…”

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

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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...

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“…14 The tryptophan-associated W3 band at ¾1558 cm 1 has two contributions. 21,22,24,25 The central feature that peaks at ¾1558 cm 1 is derived from the two A-helix tryptophans (˛14 andˇ15), whereas the ligation-sensitive shoulder at ¾1550 cm 1 originates from the allosterically important Trp37ˇ. The intensity of this shoulder is reflective of the ligation-sensitive hinge region of the˛1ˇ2 interface.…”

Section: Uv Resonance Raman Spectramentioning

confidence: 99%

“…2,10,16,25,29,30 For HbA, the wavenumber of (Fe-His) increases in the following sequence: deoxy T state 214 cm 1 , photoproduct T 218-225 cm 1 , deoxy R 220-225 cm 1 , photoproduct R 223-230 cm 1 . The wavenumber is in effect a strain gauge reflecting proximal strain or proximal enhancement at the heme.…”

Section: Visible Resonance Raman Spectra: Deoxy Derivativesmentioning

confidence: 99%

“…The wavenumber is in effect a strain gauge reflecting proximal strain or proximal enhancement at the heme. 25 Proximal strain refers to the additional energy cost of moving the iron into the heme plane on ligand binding owing to the coupling of the globin to the iron coordinate. Proximal enhancement refers to a globin-mediated reduction in the energy cost of moving the iron in plane.…”

Section: Visible Resonance Raman Spectra: Deoxy Derivativesmentioning

confidence: 99%

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Conformational and functional significance of the α140 side‐chain in HbA: a UV and visible resonance Raman study of three α140 mutants

Juszczak

Samuni

Friedman

2005

J Raman Spectroscopy

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Continuous wave UV resonance Raman (UVRR) and nanosecond time-resolved visible resonance Raman spectra were generated from the deoxy and CO derivatives of three a-chain mutants of human adult hemoglobin (HbA): Ya140F, Ya140G and Ya140A. The UVRR results show that an aromatic side-chain in the a140 site is needed for achieving the wild-type tertiary conformation in the allosterically important a 1 b 2 interface for both the deoxy T state and the liganded R state. The wavenumbers of n(Fe-His), the iron-proximal histidine stretching mode, seen in the VRR spectra from the deoxy derivatives show that the hydrogen bond between a140 tyrosine and the carbonyl of a93 valine is necessary to obtain the full quaternary constraint associated with the deoxy T state even when the a 1 b 2 interface is seemingly intact. A model is presented that describes the relationship between the packing of a cluster of residues linked to both Wb37 and Ya140 and the extent of proximal strain/quaternary constraint at the a-chain heme. The visible resonance Raman (VRR) spectra of the 8 ns photoproduct of the CO derivatives of the three mutants in the presence and absence of allosteric effectors show that all three mutants can access the R state but they show enhanced sensitivity to added IHP. The CO derivative of the Hb(Ya140F) mutant in the presence of IHP exhibits properties consistent with the high-affinity T state observed both for non-equilibrium populations of HbA isolated using sol-gel matrices and for b37 mutants where the hinge region of the a 1 b 2 interface is disrupted.

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New Light on Allostery: Dynamic Resonance Raman Spectroscopy of Hemoglobin Kempsey

Cited by 42 publications

References 35 publications

Time-resolved Absorption and UV Resonance Raman Spectra Reveal Stepwise Formation of T Quaternary Contacts in the Allosteric Pathway of Hemoglobin

Time-resolved Absorption and UV Resonance Raman Spectra Reveal Stepwise Formation of T Quaternary Contacts in the Allosteric Pathway of Hemoglobin

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

Conformational and functional significance of the α140 side‐chain in HbA: a UV and visible resonance Raman study of three α140 mutants

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