Hb Montefiore (α126(H9)Asp → Tyr). High oxygen affinity and loss of cooperativity secondary to C-terminal disruption

Henri Wajcman, Jean Kister, Frédèric Galactéros, Arthur Spielvogel, Margaret J. Lin, Gediminas J A Vidugiris, Rhoda Elison Hirsch, Joel M. Friedman, Ronald L. Nagel

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Hb Montefiore was found, in the heterozygous state, in a Puerto Rican female who had a slightly elevated total Hb level. Structural analysis revealed that Asp-α126 was replaced by Tyr. Hb Montefiore migrates close to HbF (at pH 8.6) and accounts for 20.3% of the hemolysate. Oxygen binding of red blood cells revealed a 40% decrease in the P50 (pH 7.4) and a low n value of 1.6 (normal: 2.6). Depletion of red blood cell 2,3-DPG did not change the results. Stripped Hb Montefiore at pH 7.2 showed an 8-fold reduction in P50 (0.6 versus 4.6 mm Hg) and very low cooperativity (n = 1.2 versus 2.9 for the control). Heterotopic effectors, as 2,3-diphosphoglycerate and inositol hexaphosphate had a normal effect and in addition, they increased cooperativity. The chloride ion effect and the Bohr effect were moderately reduced. A bezafibrate derivative (L345), known to bind α126, increases the P50 of HbA by 9-fold, but only by 1.5-fold that of Hb Montefiore. Combining these functional studies with intrinsic fluorescence and Resonance Raman spectroscopy, we interpret the very low n value and the high oxygen affinity for Hb Montefiore as a result of both a destabilized T state that switches to R upon ligand binding and a deoxy T state that binds ligands with higher affinity than that of deoxy HbA. Hb Montefiore still binds ligands cooperatively, but the difference in ligand binding properties of the two quaternary states has been drastically reduced.

Original languageEnglish (US)
Pages (from-to)22990-22998
Number of pages9
JournalJournal of Biological Chemistry
Volume271
Issue number38
DOIs
StatePublished - 1996

Fingerprint

Viperidae
Oxygen
Ligands
2,3-Diphosphoglycerate
L 345
Blood
Erythrocytes
Cells
Bezafibrate
Phytic Acid
Raman Spectrum Analysis
Structural analysis
Raman spectroscopy
hemoglobin Montefiore
Chlorides
Reference Values
Fluorescence
Switches
Ions
Derivatives

ASJC Scopus subject areas

  • Biochemistry

Cite this

Wajcman, H., Kister, J., Galactéros, F., Spielvogel, A., Lin, M. J., Vidugiris, G. J. A., ... Nagel, R. L. (1996). Hb Montefiore (α126(H9)Asp → Tyr). High oxygen affinity and loss of cooperativity secondary to C-terminal disruption. Journal of Biological Chemistry, 271(38), 22990-22998. https://doi.org/10.1074/jbc.271.38.22990

Hb Montefiore (α126(H9)Asp → Tyr). High oxygen affinity and loss of cooperativity secondary to C-terminal disruption. / Wajcman, Henri; Kister, Jean; Galactéros, Frédèric; Spielvogel, Arthur; Lin, Margaret J.; Vidugiris, Gediminas J A; Hirsch, Rhoda Elison; Friedman, Joel M.; Nagel, Ronald L.

In: Journal of Biological Chemistry, Vol. 271, No. 38, 1996, p. 22990-22998.

Research output: Contribution to journalArticle

Wajcman, H, Kister, J, Galactéros, F, Spielvogel, A, Lin, MJ, Vidugiris, GJA, Hirsch, RE, Friedman, JM & Nagel, RL 1996, 'Hb Montefiore (α126(H9)Asp → Tyr). High oxygen affinity and loss of cooperativity secondary to C-terminal disruption', Journal of Biological Chemistry, vol. 271, no. 38, pp. 22990-22998. https://doi.org/10.1074/jbc.271.38.22990
Wajcman, Henri ; Kister, Jean ; Galactéros, Frédèric ; Spielvogel, Arthur ; Lin, Margaret J. ; Vidugiris, Gediminas J A ; Hirsch, Rhoda Elison ; Friedman, Joel M. ; Nagel, Ronald L. / Hb Montefiore (α126(H9)Asp → Tyr). High oxygen affinity and loss of cooperativity secondary to C-terminal disruption. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 38. pp. 22990-22998.
@article{0dbf72627097489e91b5b850338f316e,
title = "Hb Montefiore (α126(H9)Asp → Tyr). High oxygen affinity and loss of cooperativity secondary to C-terminal disruption",
abstract = "Hb Montefiore was found, in the heterozygous state, in a Puerto Rican female who had a slightly elevated total Hb level. Structural analysis revealed that Asp-α126 was replaced by Tyr. Hb Montefiore migrates close to HbF (at pH 8.6) and accounts for 20.3{\%} of the hemolysate. Oxygen binding of red blood cells revealed a 40{\%} decrease in the P50 (pH 7.4) and a low n value of 1.6 (normal: 2.6). Depletion of red blood cell 2,3-DPG did not change the results. Stripped Hb Montefiore at pH 7.2 showed an 8-fold reduction in P50 (0.6 versus 4.6 mm Hg) and very low cooperativity (n = 1.2 versus 2.9 for the control). Heterotopic effectors, as 2,3-diphosphoglycerate and inositol hexaphosphate had a normal effect and in addition, they increased cooperativity. The chloride ion effect and the Bohr effect were moderately reduced. A bezafibrate derivative (L345), known to bind α126, increases the P50 of HbA by 9-fold, but only by 1.5-fold that of Hb Montefiore. Combining these functional studies with intrinsic fluorescence and Resonance Raman spectroscopy, we interpret the very low n value and the high oxygen affinity for Hb Montefiore as a result of both a destabilized T state that switches to R upon ligand binding and a deoxy T state that binds ligands with higher affinity than that of deoxy HbA. Hb Montefiore still binds ligands cooperatively, but the difference in ligand binding properties of the two quaternary states has been drastically reduced.",
author = "Henri Wajcman and Jean Kister and Fr{\'e}d{\`e}ric Galact{\'e}ros and Arthur Spielvogel and Lin, {Margaret J.} and Vidugiris, {Gediminas J A} and Hirsch, {Rhoda Elison} and Friedman, {Joel M.} and Nagel, {Ronald L.}",
year = "1996",
doi = "10.1074/jbc.271.38.22990",
language = "English (US)",
volume = "271",
pages = "22990--22998",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "38",

}

TY - JOUR

T1 - Hb Montefiore (α126(H9)Asp → Tyr). High oxygen affinity and loss of cooperativity secondary to C-terminal disruption

AU - Wajcman, Henri

AU - Kister, Jean

AU - Galactéros, Frédèric

AU - Spielvogel, Arthur

AU - Lin, Margaret J.

AU - Vidugiris, Gediminas J A

AU - Hirsch, Rhoda Elison

AU - Friedman, Joel M.

AU - Nagel, Ronald L.

PY - 1996

Y1 - 1996

N2 - Hb Montefiore was found, in the heterozygous state, in a Puerto Rican female who had a slightly elevated total Hb level. Structural analysis revealed that Asp-α126 was replaced by Tyr. Hb Montefiore migrates close to HbF (at pH 8.6) and accounts for 20.3% of the hemolysate. Oxygen binding of red blood cells revealed a 40% decrease in the P50 (pH 7.4) and a low n value of 1.6 (normal: 2.6). Depletion of red blood cell 2,3-DPG did not change the results. Stripped Hb Montefiore at pH 7.2 showed an 8-fold reduction in P50 (0.6 versus 4.6 mm Hg) and very low cooperativity (n = 1.2 versus 2.9 for the control). Heterotopic effectors, as 2,3-diphosphoglycerate and inositol hexaphosphate had a normal effect and in addition, they increased cooperativity. The chloride ion effect and the Bohr effect were moderately reduced. A bezafibrate derivative (L345), known to bind α126, increases the P50 of HbA by 9-fold, but only by 1.5-fold that of Hb Montefiore. Combining these functional studies with intrinsic fluorescence and Resonance Raman spectroscopy, we interpret the very low n value and the high oxygen affinity for Hb Montefiore as a result of both a destabilized T state that switches to R upon ligand binding and a deoxy T state that binds ligands with higher affinity than that of deoxy HbA. Hb Montefiore still binds ligands cooperatively, but the difference in ligand binding properties of the two quaternary states has been drastically reduced.

AB - Hb Montefiore was found, in the heterozygous state, in a Puerto Rican female who had a slightly elevated total Hb level. Structural analysis revealed that Asp-α126 was replaced by Tyr. Hb Montefiore migrates close to HbF (at pH 8.6) and accounts for 20.3% of the hemolysate. Oxygen binding of red blood cells revealed a 40% decrease in the P50 (pH 7.4) and a low n value of 1.6 (normal: 2.6). Depletion of red blood cell 2,3-DPG did not change the results. Stripped Hb Montefiore at pH 7.2 showed an 8-fold reduction in P50 (0.6 versus 4.6 mm Hg) and very low cooperativity (n = 1.2 versus 2.9 for the control). Heterotopic effectors, as 2,3-diphosphoglycerate and inositol hexaphosphate had a normal effect and in addition, they increased cooperativity. The chloride ion effect and the Bohr effect were moderately reduced. A bezafibrate derivative (L345), known to bind α126, increases the P50 of HbA by 9-fold, but only by 1.5-fold that of Hb Montefiore. Combining these functional studies with intrinsic fluorescence and Resonance Raman spectroscopy, we interpret the very low n value and the high oxygen affinity for Hb Montefiore as a result of both a destabilized T state that switches to R upon ligand binding and a deoxy T state that binds ligands with higher affinity than that of deoxy HbA. Hb Montefiore still binds ligands cooperatively, but the difference in ligand binding properties of the two quaternary states has been drastically reduced.

UR - http://www.scopus.com/inward/record.url?scp=0029661440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029661440&partnerID=8YFLogxK

U2 - 10.1074/jbc.271.38.22990

DO - 10.1074/jbc.271.38.22990

M3 - Article

VL - 271

SP - 22990

EP - 22998

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 38

ER -