Structural characterization of an Ascaris myoglobin.

Blaxter, Mark; Vanfleteren, Jacques R.; Xia, Jia-Zhi; Moëns, Luc

doi:10.1016/s0021-9258(18)43794-5

Cited by 25 publications

(5 citation statements)

References 33 publications

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“…Monomeric cytoplasmic Hbs and Mbs exhibit a large variation in oxygen affinities. Paramecium Hb exhibits a moderate oxygen affinity, similar to that of sperm whale Mb but different from the extremely high affinities of many truncated Hbs (Table ) and of nematode, trematode, and other nonvertebrate Hbs and Mbs ( − ).…”

Section: Discussionmentioning

confidence: 81%

Ligand Binding in the Ferric and Ferrous States of Paramecium Hemoglobin

et al. 2000

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The unicellular protozoan Paramecium caudatum contains a monomeric hemoglobin (Hb) that has only 116 amino acid residues. This Hb shares the simultaneous presence of a distal E7 glutamine and a B10 tyrosine with several invertebrate Hbs. In the study presented here, we have used ligand binding kinetics and resonance Raman spectroscopy to characterize the effect of the distal pocket residues of Paramecium Hb in stabilizing the heme-bound ligands. In the ferric state, the high-spin to low-spin (aquo-hydroxy) transition takes place with a pK(a) of approximately 9.0. The oxygen affinity (P(50) = 0.45 Torr) is similar to that of myoglobin. The oxygen on- and off-rates are also similar to those of sperm whale myoglobin. Resonance Raman data suggest hydrogen bonding stabilization of bound oxygen, evidenced by a relatively low frequency of Fe-OO stretching (563 cm(-1)). We propose that the oxy complex is an equilibrium mixture of a hydrogen-bonded closed structure and an open structure. Oxygen will dissociate preferentially from the open structure, and therefore, the fraction of open structure population controls the rate of oxygen dissociation. In the CO complex, the Fe-CO stretching frequency at 493 cm(-1) suggests an open heme pocket, which is consistent with the higher on- and off-rates for CO relative to those in myoglobin. A high rate of ligand binding is also consistent with the observation of an Fe-histidine stretching frequency at 220 cm(-1), indicating the absence of significant proximal strain. We postulate that the function of Paramecium Hb is to supply oxygen for cellular oxidative processes.

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Section: Discussionmentioning

confidence: 81%

Ligand Binding in the Ferric and Ferrous States of Paramecium Hemoglobin

et al. 2000

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“…In addition to the perienteric hemoglobin that is the subject of this review, Ascaris possesses at least one and perhaps several body wall globins. ,,− They appear to be disulfide-linked dimers that can be reduced to 15−17 kDa monomers . Thus, the polypeptides are one-half the size of the perienteric hemoglobin.…”

Section: Body Wall Hemoglobinmentioning

confidence: 99%

“…The oxygen affinity of the most abundant form has been measured and is nearly 2 orders of magnitude less than that of the perienteric hemoglobin 7,19 but still an order of magnitude stronger than that of sperm whale myoglobin, again due to a slow dissociation rate. The amino acid sequence has a B10 tyrosine and an E7 glutamine, analogous to the perienteric molecule …”

Section: Body Wall Hemoglobinmentioning

confidence: 99%

“…7,19,[36][37][38][39] They appear to be disulfide-linked dimers that can be reduced to 15-17 kDa monomers. 40 Thus, the polypeptides are one-half the size of the perienteric hemoglobin. The oxygen affinity of the most abundant form has been measured and is nearly 2 orders of magnitude less than that of the perienteric hemoglobin 7,19 but still an order of magnitude stronger than that of sperm whale myoglobin, again due to a slow dissociation rate.…”

Section: Body Wall Hemoglobinmentioning

confidence: 99%

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Oxygen-Avid Hemoglobin of Ascaris

Goldberg

1999

Chem. Rev.

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Dr. Goldberg did his undergraduate training at Harvard University, where he studied with Eugene Kennedy. He then performed doctoral work with Stuart Kornfeld and received his M.D./Ph.D. degree from Washington University in 1985. After a residency in internal medicine at the Brigham and Women's Hospital in Boston and an infectious diseases fellowship at Washington University, he did postdoctoral research with Anthony Cerami at Rockefeller University before joining the faculty at Washington University in 1990. He is currently professor of medicine with a joint appointment in molecular microbiology and is associate investigator in the Howard Hughes Medical Institute. Dr. Goldberg is interested in the biochemistry and chemotherapy of parasitic diseases. His work has focused on hemoglobin degradation and heme polymerization in the malaria parasite Plasmodium falciparum, as well as structure and function of Ascaris perienteric hemoglobin.

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“…We chose the mutants shown in Figure that differ in their capacity to form H-bonds to the bound NO x ligands (wt with one H-bonding residue, H64A with zero H-bonding residues, H64Q with one H-bonding residue, and V68A/I107Y with two H-bonding residues), which to the best our knowledge is the first systematic structural investigation of different H-bonding capacities on NO orientations in the heme distal pocket, including some new patterns not reported previously. The H64Q mutant is an analogue of the wt Mbs from certain species of worms, , elephants, , and sharks − and of the α chains of opossum Hbs . Alternatively, the H64A mutant is related to the Mbs that have hydrophobic residues (Val and Leu) at this E7 position. − We hypothesized that the introduction of the potential second H-bond interaction in the V68A/I107Y double mutant would help stabilize the V-shaped N -nitro binding mode as observed in cyt cd 1 NiRs.…”

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confidence: 99%

Nitrosyl Myoglobins and Their Nitrite Precursors: Crystal Structural and Quantum Mechanics and Molecular Mechanics Theoretical Investigations of Preferred Fe–NO Ligand Orientations in Myoglobin Distal Pockets

et al. 2018

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The globular dioxygen binding heme protein myoglobin (Mb) is present in several species. Its interactions with the simple nitrogen oxides, namely, nitric oxide (NO) and nitrite, have been known for decades, but the physiological relevance has only recently become more fully appreciated. We previously reported the O-nitrito mode of binding of nitrite to ferric horse heart wild-type (wt) Mb and human hemoglobin. We have expanded on this work and report the interactions of nitrite with wt sperm whale (sw) Mb and its H64A, H64Q, and V68A/I107Y mutants whose dissociation constants increase in the following order: H64Q < wt < V68A/I107Y < H64A. We also report their X-ray crystal structures that reveal the O-nitrito mode of binding of nitrite to these derivatives. The Mb-mediated reductions of nitrite to NO and structural data for the wt and mutant Mb-NOs are described. We show that their FeNO orientations vary with distal pocket identity, with the FeNO moieties pointing toward the hydrophobic interiors when the His64 residue is present but toward the hydrophilic exterior when this His64 residue is absent in this set of mutants. This correlates with the nature of H-bonding to the bound NO ligand (nitrosyl O vs N atom). Quantum mechanics and hybrid quantum mechanics and molecular mechanics calculations help elucidate the origin of the experimentally preferred NO orientations. In a few cases, the calculations reproduce the experimentally observed orientations only when the whole protein is taken into consideration.

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Structural characterization of an Ascaris myoglobin.

Cited by 25 publications

References 33 publications

Ligand Binding in the Ferric and Ferrous States of Paramecium Hemoglobin

Ligand Binding in the Ferric and Ferrous States of Paramecium Hemoglobin

Oxygen-Avid Hemoglobin of Ascaris

Nitrosyl Myoglobins and Their Nitrite Precursors: Crystal Structural and Quantum Mechanics and Molecular Mechanics Theoretical Investigations of Preferred Fe–NO Ligand Orientations in Myoglobin Distal Pockets

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