Serine92 (F7) contributes to the control of heme reactivity and stability in myoglobin

Smerdon, Stephen J.; Krzywda, Szymon; Wilkinson, Anthony J.; Brantley, R E; Carver, Theodore E.; Hargrove, Mark S.; Olson, John S.

doi:10.1021/bi00070a023

Cited by 85 publications

(94 citation statements)

References 26 publications

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“…The strength of the hydrogen bond formed by a nitrogen proton in the proximal histidine and the polarity of the environment are powerful factors for determining the Fe-His stretching frequency in the heme-histidine moiety. This hydrogen bonding network in hemoglobins and myoglobins has also been also related to ligand affinity (37,40). The significant differences observed in the heme-ligand dissociation rate constants between Mb and Hb Asc have mainly been attributed to the tilted orientation of the His(F8) with regard to the pyrrole rings of the heme (45).…”

Section: Discussionmentioning

confidence: 94%

“…3). This last pair of amino acids has been proposed to stabilize the oxygenated form of HbII LP by means of strong and weak hydrogen bonds, respectively (37,40). Hb Asc also has a Tyr(B10) and a Gln(E7), and a high oxygen affinity and unusually slow off rate for oxygen dissociation (15,41).…”

Section: Discussionmentioning

confidence: 99%

“…1). The tetrameric Hb IIAB,Si in the form of two heterodimers is composed by chains Hb IIA,Si and Hb IIB,Si (37). The hypothetical HbII LP tetramer in the unit cell is different from that of the S. inaequivalvis hemoglobin.…”

Section: Hbii Lp Structure and Sequence Analysis-thementioning

confidence: 96%

“…The orientation of the proximal His 97 (F15) is roughly perpendicular to the heme plane and the average distance between the His 97 (NE2) atom and the iron atom is 2.06 Å, which is a slightly shorter distance when compared with the sulfide (PDB code 1MOH), cyanide (PDB codes 1ETB and 1B0B), and water-bound HbI LP , where the distances range from 2.13 to 2.31 Å. It has been suggested that within the various kinds of hemoglobin and myoglobin a hydrogen bond between the proximal histidine His(F8) and the side chain of a residue next to it modulates the strength of the His-Fe bond, regulating the ligand affinity (37,40). In HbII LP , His(F8) has two possible hydrogen bond interactions, the first one with the buried water molecule and the second one from the interaction of the carbonyl group of Met 93 and the ND1 from histidine ( Table 2).…”

Section: Hbii Lp Distal and Proximal Heme Pocket-mentioning

confidence: 99%

See 3 more Smart Citations

Structure and Ligand Selection of Hemoglobin II from Lucina pectinata

Gavira

Cámara-Artigas

Jesús-Bonilla

et al. 2008

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Hbii Lp Structure and Sequence Analysis-thementioning

confidence: 96%

Section: Hbii Lp Distal and Proximal Heme Pocket-mentioning

confidence: 99%

See 2 more Smart Citations

Structure and Ligand Selection of Hemoglobin II from Lucina pectinata

Gavira

Cámara-Artigas

Jesús-Bonilla

et al. 2008

Journal of Biological Chemistry

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“…Smerdon and co-workers have measured a small difference in CO recombination kinetics in the pig myoglobin mutant S92A, where the hydrogen bond between the proximal histidine and Ser 92 is removed (Smerdon et al, 1993), though the changes are smaller than those observed by replacement of 4-MeIm with N-MeIm in H93G. This might be because the histidine in wild type myoglobin hydrogen bonds with both Ser 92 and the backbone carbonyl of Leu 89 (Cheng & Shoenborn, 1991).…”

Section: Mechanism Of Ligand Exchange In H93g(l)comentioning

confidence: 99%

Modulation of Protein Function by Exogenous Ligands in Protein Cavities: CO Binding to a Myoglobin Cavity Mutant Containing Unnatural Proximal Ligands

1996

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A variety of heterocyclic ligands can be exchanged into the proximal cavity of sperm whale myoglobin mutant H93G, providing a simple method for introduction of the equivalent of unnatural amino acid side chains into a functionally critical location in this protein. These modified proteins bind CO on the distal side. 1 H NMR data on H93G(Im)CO, where Im is imidazole, demonstrate that the structure of the distal heme pocket in H93G(Im)CO is very similar to that of wild type; thus, the effects of the proximal ligand's properties on CO binding can be studied with minimal perturbation of distal pocket structure. The exogenous proximal ligands used in this study include imidazole (Im), 4-methylimidazole (4-MeIm), 4-bromoimidazole (4-BrIm), N-methylimidazole (N-MeIm), pyridine (Pyr), and 3-fluoropyridine (3-FPyr). Substitution of the proximal ligand is found to produce substantial changes in the CO on and off rates, the equilibrium binding constant, and the vibrational stretch frequency of CO. Many of the changes are as large as those reported for distal pocket mutants prepared by site-directed mutagenesis. The ability to systematically vary the nature of the proximal ligand is exploited to test the effects of particular properties of the proximal ligand on CO binding. For example, 4-MeIm and 4-BrIm are similar in size and shape but differ significantly in pK a . The same relationship is true for Pyr and 3-FPyr. By comparison of the IR spectra and CO recombination kinetics of these complexes, the effects of proximal ligand pK a on the CO binding are assessed. Likewise, N-MeIm and 4-MeIm are similar in size and pK a but differ in their ability to hydrogen bond to amino acid residues in the proximal cavity. Comparisons of IR spectra and CO binding kinetics in these complexes reveal that proximal ligand conformation and hydrogen bonding affect the kinetics of CO binding. The mechanism of proximal ligand exchange between solution and the proximal cavity in CO complexes was investigated by obtaining the 19 F NMR spectrum of H93G(3-FPyr)CO, whose 19 F signal can be observed without interference from resonances of the protein. The proximal ligand is found to exchange within a few seconds by saturation transfer. This exchange rate is about 2 orders of magnitude faster than what is observed for the isoelectronic metcyano complex [Decatur, S. M., & Boxer, S. G. (1995) Biochemistry 34, 2122-2129; in both the ferrous CO and ferric cyano complexes, the proximal ligand exchange rate is independent of ligand concentration. These results suggest that the rate-limiting step in proximal ligand exchange is breakage of the iron-ligand bond, followed by rapid diffusion of the ligand through the protein to bulk solution.

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Trans-substitution of the proximal hydrogen bond in myoglobin: I. Structural consequences of hydrogen bond deletion

Barrick

Dahlquist

2000

Proteins

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The structural role of a side-chain to side-chain protein hydrogen bond is examined using trans-substitution of the proximal histidine of myoglobin with methylimidazoles (Barrick, Biochemistry 1994;33:6546-6554). Modification of the chemical structure of exogenous ligands allows this hydrogen bond to be disrupted. Comparison of the crystal structures of H93G myoglobin complexed 4-methylimidazole (4meimd; methylation at carbon 4) and 1-methylimidazole (1meimd; methylation at the adjacent nitrogen, preventing hydrogen bonding between the imidazole ligand and the protein) shows that the polypeptide, heme, and methylimidazole orientations are the same within error. For 4meimd there appear to be major and minor conformations corresponding to different tautomeric states of the ligand. Conformational heterogeneity is also seen in the hyperfine-shifted region of the NMR spectrum of 4meimd complexed with high-spin H93G deoxyMb. The major conformation of the 4meimd ligand and the 1meimd ligand, as seen in the respective crystal structures, are quite similar except that the proximal ligand NH-to-Ser92-OH hydrogen bond is eliminated in the 1meimd complex, and instead the proximal ligand CH is adjacent to the Ser92-OH. Thus, this system provides a means to eliminate the Mb proximal hydrogen bond in a chemically and structurally conservative way.

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Serine92 (F7) contributes to the control of heme reactivity and stability in myoglobin

Cited by 85 publications

References 26 publications

Structure and Ligand Selection of Hemoglobin II from Lucina pectinata

Structure and Ligand Selection of Hemoglobin II from Lucina pectinata

Modulation of Protein Function by Exogenous Ligands in Protein Cavities: CO Binding to a Myoglobin Cavity Mutant Containing Unnatural Proximal Ligands

Trans-substitution of the proximal hydrogen bond in myoglobin: I. Structural consequences of hydrogen bond deletion

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