The 2.7 Å crystal structure of deoxygenated hemoglobin from the sea lamprey (Petromyzon marinus): structural basis for a lowered oxygen affinity and Bohr effect

Heaslet, H.; Royer, William E.

doi:10.1016/s0969-2126(99)80068-9

Cited by 35 publications

(39 citation statements)

References 32 publications

(42 reference statements)

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“…This response is opposite to that of human hemoglobin, where water stabilizes the oxygenated, high-affinity state of the hemoglobin, but similar to that found in the dimeric hemoglobin from the gastropod mollusc Scapharca inaequivalvis, where 6-8 water molecules bind at the dimer interface in the deoxy conformation (Royer et al, 1996). Interestingly, the recently solved crystal structure of dimeric (deoxy) hagfish hemoglobin (Mito et al, 2002) indicates a subunit arrangement similar (but not identical) to that of lamprey and dimeric Scapharca hemoglobins, with the two heme groups in close contact with each other (Heaslet and Royer, 1999;Royer, 1994).…”

Section: Discussionsupporting

confidence: 54%

“…In lampreys, monomeric hemoglobins similarly associate upon deoxygenation, and erythrocyte shrinking (with the consequent increase in protein concentration) decreases O2 affinity (Airaksinen and Nikinmaa, 1995); this is in contrast to hagfish red blood cells, suggesting that lamprey hemoglobins have little or no sensitivity to changes in water activity. Accordingly, no water molecules were detected at the dimeric interface of the deoxy form of the lamprey Petromyzon marinus HbV (Heaslet and Royer, 1999), although this could be due to the fairly low resolution of the crystallographic structure (2.7·Å).…”

Section: Discussionmentioning

confidence: 89%

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Water regulates oxygen binding in hagfish (Myxine glutinosa)hemoglobin

Müller

Fago

Weber

2003

Journal of Experimental Biology

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SUMMARY Hagfish hemoglobin (Hb) is considered to represent a transition stage between invertebrate and vertebrate hemoglobins. The Hb system of Myxine glutinosa consists of three monomeric hemoglobins, which upon deoxygenation associate to form primarily heterodimers and heterotetramers. Myxine glutinosa is an osmoconformer, whose red blood cells show the exceptional ability to swell and remain swollen under hyposmotic conditions. In order to determine whether water activity regulates hemoglobin function,the effect of changes in osmolality on hemoglobin-O2 affinity was investigated by applying the osmotic stress method to purified hemoglobins as well as intact red blood cells. Oxygen affinity decreases when water activity increases, indicating that water molecules stabilize the low-affinity,oligomeric state of the hemoglobin. This effect is opposite to that observed in tetrameric vertebrate hemoglobins, but resembles that seen in the dimeric hemoglobin of the marine clam Scapharca inaequivalvis. Our data show that water may act as an allosteric effector for hemoglobin within intact red cells and even in animals that do not experience large variations in blood osmolality.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 89%

Water regulates oxygen binding in hagfish (Myxine glutinosa)hemoglobin

Müller

Fago

Weber

2003

Journal of Experimental Biology

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“…The six unique dimers in the monoclinic crystals formed two essentially indistinguishable hexamers arranged as one turn of an approximately 3-fold screw axis (4). A nearly identical hexameric assemblage is also observed in the deoxy orthorhombic crystals.…”

Section: Resultsmentioning

confidence: 83%

“…Only subtle changes in the position of distal residues are observed upon ligand binding. Bottom panel, in lamprey hemoglobin V, the distal histidine (yellow with blue nitrogen atoms) is in close proximity to the heme iron in the dimeric deoxy state (left column), sterically restricting ligand binding (4). In the monomeric cyano-met form (6) (right column), it has moved away from the ligand binding site and rotated to a position that allows the formation of a stabilizing hydrogen bond with bound ligand.…”

Section: Fig 6 Proximal Versus Distal Regulation Of Oxygen Affinitymentioning

confidence: 99%

“…In contrast, there were no major structural changes on the opposite (proximal) side of the heme group. These results lead to the hypothesis that oxygen affinity in lamprey hemoglobin primarily is regulated distally (4). The distal regulation of oxygen affinity in lamprey hemoglobin is far different from that believed to be operative in other cooperative hemoglobins such as human hemoglobin (1,7) and Scapharca hemoglobin (8) in which proximal effects appear to play a central role.…”

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confidence: 92%

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Crystalline Ligand Transitions in Lamprey Hemoglobin

Heaslet¹,

Royer²

2001

Journal of Biological Chemistry

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The hemoglobins of the Sea Lamprey (Petromyzon marinus) exist in an equilibrium between low affinity oligomers, stabilized by proton binding, and higher affinity monomers, stabilized by oxygen binding. Recent crystallographic analysis revealed that dimerization is coupled with key changes at the ligand binding site with the distal histidine sterically restricting ligand binding in the deoxy dimer but with no significant structural rearrangements on the proximal side. These structural insights led to the hypothesis that oxygen affinity of lamprey hemoglobin is distally regulated. Here we present the 2.9-Å crystal structure of deoxygenated lamprey hemoglobin in an orthorhombic crystal form along with the structure of these crystals exposed to carbon monoxide. The hexameric assemblage in this crystal form is very similar to those observed in the previous deoxy structure. Whereas the hydrogen bonding network and packing contacts formed in the dimeric interface of lamprey hemoglobin are largely unaffected by ligand binding, the binding of carbon monoxide induces the distal histidine to swing to positions that would preclude the formation of a stabilizing hydrogen bond with the bound ligand. These results suggest a dual role for the distal histidine and strongly support the hypothesis that ligand affinity in lamprey hemoglobin is distally regulated.

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Molecular modelling ofTrematomus newnesi Hb 1: Insights for a lowered oxygen affinity and lack of root effect

D’Avino¹,

Luca²

2000

Proteins

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Three-dimensional structural models of the hemoglobin (Hb 1) of the Antarctic fish Trematomus newnesi were built by homology modelling, using as template the X-ray crystallographic structures of Trematomus (previously named Pagothenia) bernacchii Hb 1, both in R and T state. The Hbs of these two fishes, although showing remarkably different oxygen binding properties, differ only by 4 residues in the alpha chain (142 aa) and 10 residues in the beta chain (146 aa). T. newnesi Hb1 R-state model, essentially performed as a quality control of the adopted modelling procedure, showed a good correspondence with the crystallographic one. Modelling of T. newnesi Hb1 in the T state was performed taking into account that the proton uptake by aspartate residues, proposed to be responsible for half of the Root effect in T. bernacchii Hb 1 (showing sharp pH dependent oxygen affinity and T-state overstabilization at low pH, i. e. Bohr and Root effect), does not occur in T. newnesi Hb1 (having nearly pH-independent lower oxygen affinity). Comparison with the template structure (submitted to the same minimization procedure) indicates that, in T. newnesi Hb1 T-state model, the substitution of Ile for Thr in 41 C6, in central position of the switch region, induces at the alpha(1)beta(2) interface structural modifications able to hamper the protonation. Similar modifications are also found in T. bernacchii Hb 1 modelled in the T state with the single substitution Thr-->Ile in 41alpha. These models also suggest that the lower oxygen affinity observed in T. newnesi Hb1 is related to structural differences at the alpha(1)beta(2) interface leading to a more stable low-affinity T state. Proteins 2000;39:155-165.

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The 2.7 Å crystal structure of deoxygenated hemoglobin from the sea lamprey (Petromyzon marinus): structural basis for a lowered oxygen affinity and Bohr effect

Cited by 35 publications

References 32 publications

Water regulates oxygen binding in hagfish (Myxine glutinosa)hemoglobin

Water regulates oxygen binding in hagfish (Myxine glutinosa)hemoglobin

Crystalline Ligand Transitions in Lamprey Hemoglobin

Molecular modelling ofTrematomus newnesi Hb 1: Insights for a lowered oxygen affinity and lack of root effect

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