Ligand binding to synthetic mutant myoglobin (His-E7----Gly): role of the distal histidine.

Braunstein, D.; Ansari, Anjum; Berendzen, Joel; Cowen, B. R.; Egeberg, Karen D.; Frauenfelder, Hans; Hong, Mineui; Ormos, Pál; Sauke, Todd B.; Scholl, Reinhard

doi:10.1073/pnas.85.22.8497

Cited by 77 publications

(41 citation statements)

References 36 publications

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“…Similar frequencies are also observed when HisE7 is replaced with apolar amino acids incapable of hydrogen bonding with the bound ligand Park et al, 1999). Upon photodissociation of MbCO at cryogenic temperatures, ligands cannot escape from the protein and migrate to internal cavities in the protein that serve as specific docking sites (Chu et al, 2000;Ostermann et al, 2000;Bourgeois et al, 2003;Schotte et al, 2003;Schmidt et al, 2005), as inferred from the appearance of sharp bands of the photodissociated CO between 2100 and 2200 cm −1 (Alben et al, 1982;Braunstein et al, 1988;Braunstein et al, 1993;Mourant et al, 1993). Three docking sites labeled B, C, and D can be distinguished by their characteristic CO stretching spectra (Nienhaus et al, 2003b;Nienhaus et al, 2003a;Nienhaus et al, 2003c).For an individual site, a specific doublet of IR bands is frequently observed due to the vibrational Stark effect, the effect of an electric field on a vibrational transition, and the doublet indicates that the CO molecules are trapped in opposite orientations (Kriegl et al, 2003;Lehle et al, 2005;Nienhaus et al, 2005).…”

Section: Introductionmentioning

confidence: 54%

Transient ligand docking sites in Cerebratulus lacteus mini-hemoglobin

Deng

Nienhaus

Palladino

et al. 2007

Gene

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The monomeric hemoglobin of the nemertean worm Cerebratulus lacteus functions as an oxygen storage protein to maintain neural activity under hypoxic conditions. It shares a large, apolar matrix tunnel with other small hemoglobins, which has been implicated as a potential ligand migration pathway. Here we explore ligand migration and binding within the distal heme pocket, to which the tunnel provides access to ligands from the outside. FTIR/TDS experiments performed at cryogenic temperatures reveal the presence of three transient ligand docking sites within the distal pocket, the primary docking site B on top of pyrrole C and secondary sites C and D. Site C is assigned to a cavity adjacent to the distal portion of the heme pocket, surrounded by the B and E helices. It has an opening to the apolar tunnel and is expected to be on the pathway for ligand entry and exit, whereas site D, circumscribed by TyrB10, GlnE7, and the CD corner, most likely is located on a side pathway of ligand migration. Flash photolysis experiments at ambient temperatures indicate that the rate-limiting step for ligand binding to CerHb is migration through the apolar channel to site C. Movement from C to B and iron-ligand bond formation involve low energy barriers and thus are very rapid processes in the wt protein.

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Section: Introductionmentioning

confidence: 54%

Transient ligand docking sites in Cerebratulus lacteus mini-hemoglobin

Deng

Nienhaus

Palladino

et al. 2007

Gene

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“…Limited IR data has been published for other Mb and Hb mutants, and some comparisons can be made. The IR spectrum of the mutant H64G in SW Mb at 10 K is unusually broad and peaks at 1973 cm- (38). For human Mb H64A, two closely spaced peaks are observed (Fig.…”

Section: Resultsmentioning

confidence: 97%

Perturbations of the distal heme pocket in human myoglobin mutants probed by infrared spectroscopy of bound CO: correlation with ligand binding kinetics.

Balasubramanian

Lambright

Boxer

1993

Proc. Natl. Acad. Sci. U.S.A.

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The infrared spectra of CO bound to human myoglobin and myoglobin mutants at positions His-64, Val-68, Asp-60, and Lys-45 on the distal side have been measured between 100 and 300 K. Large differences are observed with mutations at His-64 and Val-68 as weli as with temperature and pH. Although distal His-64 is found to affect CO bonding, Val-68 also plays a major role. The variations are analyzed qualitatively in terms of a simple model involving steric interaction between the bound CO and the distal residues. A strong correlation is found between the final barrier height to CO recombination and the CO stretch frequency: as compared to wild type, the barrier is smaller in those mutants that have a higher CO stretch frequency (vCO) and vice versa. Possible reasons for this correlation are discussed. It is emphasized that the temperature and pH dependence of both the kinetics and the infrared spectra must be measured to obtain a consistent picture.

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“…It is usually attributed to an "open pocket" conformer in which the distal histidine has rotated away from the ligand enough to reduce the electrostatic interaction with its positively charged imidazole side chain (27,28). For both the V(E11)T mutants, the A 0 conformer accounts for ϳ25% of the total intensity; it appears at 1968.2 cm Ϫ1 for ␤V(E11)T and at 1964.7 cm Ϫ1 for ␣V(E11)T.…”

Section: Resultsmentioning

confidence: 99%

Properties of Human Hemoglobins with Increased Polarity in the α- or β-Heme Pocket

Karavitis

Fronticelli

Brinigar

et al. 1998

Journal of Biological Chemistry

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The spectroscopic, conformational, and functional properties of mutant carbonmonoxy hemoglobins in which either the ␤-globin Val 67 (E11) or the ␣-globin Val 62 (E11) is replaced by threonine have been investigated. The thermal evolution of the Soret absorption band and the stretching frequency of the bound CO were used to probe the stereodynamic properties of the heme pocket. The functional properties were investigated by kinetic measurements. The spectroscopic and functional data were related to the conformational properties through molecular analysis. The effects of this nonpolar-to-polar isosteric mutation are: (i) increase of heme pocket anharmonic motions, (ii) stabilization of the A 0 conformer in the IR spectrum, (iii) increased CO dissociation rates. The spectroscopic data indicate that for the carbonmonoxy derivatives, the Val 3 Thr mutation has a larger conformational effect on the ␤-subunits than on the ␣-subunits. This is at variance with the deoxy derivatives where the conformational modification was larger in the heme pocket of the ␣-subunit (Cupane, A., Leone, M., Militello, V., Friedman, R. K., Koley, A. P., Vasquez, G. P., Brinigar, W. S., Karavitis, M., and Fronticelli, C. (1997) J. Biol. Chem. 272, 26271-26278). These effects are attributed to a different electrostatic interaction between O ␥ of Thr(E11) and the bound CO molecule. Molecular analysis indicates a more favorable interaction of the bound CO with Thr O ␥ in the ␤-subunit heme pocket.

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Ligand binding to synthetic mutant myoglobin (His-E7----Gly): role of the distal histidine.

Cited by 77 publications

References 36 publications

Transient ligand docking sites in Cerebratulus lacteus mini-hemoglobin

Transient ligand docking sites in Cerebratulus lacteus mini-hemoglobin

Perturbations of the distal heme pocket in human myoglobin mutants probed by infrared spectroscopy of bound CO: correlation with ligand binding kinetics.

Properties of Human Hemoglobins with Increased Polarity in the α- or β-Heme Pocket

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