A potential determinant of enhanced crystallization of HbC

Spectroscopic and functional evidence of an alteration in the central cavity of oxyHbC

Rhoda Elison Hirsch, Anne C. Rybicki, Nazim A. Fataliev, Margaret J. Lin, Joel M. Friedman, Ronald L. Nagel

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The structural basis of the crystallizing tendencies of oxyHbC (β6Glu → Lys), that produces haemolytic anaemia in homozygotes, is unknown. Using a fluorescent organic phosphate analogue (8-hydroxy-1,3,6-pyrenetrisulphonate), and conventional oxygen equilibrium studies, data suggest that the binding of inositolhexaphosphate (IHP) to oxyHbC differs from HbA, indicating perturbations of the oxyHbC central cavity, which was predicted from our earlier spectroscopic findings. To define the relationship between this conformational change in oxyHbC and its tendency to crystallize, the effect of four central cavity ligands on the crystallization rate was studied: a peptide containing 11 residues from the N-terminal portion of band 3, the full cytoplasmic domain of band 3, 2,3-diphosphoglycerate and IHP. OxyHbC crystallization was accelerated by all these central cavity ligands and not by the appropriate controls. These central cavity changes become an excellent candidate for the dramatic increase in the crystallization rate of oxyHbC.

Original languageEnglish (US)
Pages (from-to)583-588
Number of pages6
JournalBritish Journal of Haematology
Volume98
Issue number3
StatePublished - 1997

Fingerprint

Crystallization
Ligands
2,3-Diphosphoglycerate
Organophosphates
Hemolytic Anemia
Homozygote
Oxygen
Peptides

Keywords

  • Band 3
  • Crystallization kinetics
  • Diphosphoglyceric acid
  • Fluorescence
  • HbC

ASJC Scopus subject areas

  • Hematology

Cite this

A potential determinant of enhanced crystallization of HbC : Spectroscopic and functional evidence of an alteration in the central cavity of oxyHbC. / Hirsch, Rhoda Elison; Rybicki, Anne C.; Fataliev, Nazim A.; Lin, Margaret J.; Friedman, Joel M.; Nagel, Ronald L.

In: British Journal of Haematology, Vol. 98, No. 3, 1997, p. 583-588.

Research output: Contribution to journalArticle

Hirsch, Rhoda Elison ; Rybicki, Anne C. ; Fataliev, Nazim A. ; Lin, Margaret J. ; Friedman, Joel M. ; Nagel, Ronald L. / A potential determinant of enhanced crystallization of HbC : Spectroscopic and functional evidence of an alteration in the central cavity of oxyHbC. In: British Journal of Haematology. 1997 ; Vol. 98, No. 3. pp. 583-588.
@article{a9fbb6db1e2f4cf8b89d999e72df1310,
title = "A potential determinant of enhanced crystallization of HbC: Spectroscopic and functional evidence of an alteration in the central cavity of oxyHbC",
abstract = "The structural basis of the crystallizing tendencies of oxyHbC (β6Glu → Lys), that produces haemolytic anaemia in homozygotes, is unknown. Using a fluorescent organic phosphate analogue (8-hydroxy-1,3,6-pyrenetrisulphonate), and conventional oxygen equilibrium studies, data suggest that the binding of inositolhexaphosphate (IHP) to oxyHbC differs from HbA, indicating perturbations of the oxyHbC central cavity, which was predicted from our earlier spectroscopic findings. To define the relationship between this conformational change in oxyHbC and its tendency to crystallize, the effect of four central cavity ligands on the crystallization rate was studied: a peptide containing 11 residues from the N-terminal portion of band 3, the full cytoplasmic domain of band 3, 2,3-diphosphoglycerate and IHP. OxyHbC crystallization was accelerated by all these central cavity ligands and not by the appropriate controls. These central cavity changes become an excellent candidate for the dramatic increase in the crystallization rate of oxyHbC.",
keywords = "Band 3, Crystallization kinetics, Diphosphoglyceric acid, Fluorescence, HbC",
author = "Hirsch, {Rhoda Elison} and Rybicki, {Anne C.} and Fataliev, {Nazim A.} and Lin, {Margaret J.} and Friedman, {Joel M.} and Nagel, {Ronald L.}",
year = "1997",
language = "English (US)",
volume = "98",
pages = "583--588",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - A potential determinant of enhanced crystallization of HbC

T2 - Spectroscopic and functional evidence of an alteration in the central cavity of oxyHbC

AU - Hirsch, Rhoda Elison

AU - Rybicki, Anne C.

AU - Fataliev, Nazim A.

AU - Lin, Margaret J.

AU - Friedman, Joel M.

AU - Nagel, Ronald L.

PY - 1997

Y1 - 1997

N2 - The structural basis of the crystallizing tendencies of oxyHbC (β6Glu → Lys), that produces haemolytic anaemia in homozygotes, is unknown. Using a fluorescent organic phosphate analogue (8-hydroxy-1,3,6-pyrenetrisulphonate), and conventional oxygen equilibrium studies, data suggest that the binding of inositolhexaphosphate (IHP) to oxyHbC differs from HbA, indicating perturbations of the oxyHbC central cavity, which was predicted from our earlier spectroscopic findings. To define the relationship between this conformational change in oxyHbC and its tendency to crystallize, the effect of four central cavity ligands on the crystallization rate was studied: a peptide containing 11 residues from the N-terminal portion of band 3, the full cytoplasmic domain of band 3, 2,3-diphosphoglycerate and IHP. OxyHbC crystallization was accelerated by all these central cavity ligands and not by the appropriate controls. These central cavity changes become an excellent candidate for the dramatic increase in the crystallization rate of oxyHbC.

AB - The structural basis of the crystallizing tendencies of oxyHbC (β6Glu → Lys), that produces haemolytic anaemia in homozygotes, is unknown. Using a fluorescent organic phosphate analogue (8-hydroxy-1,3,6-pyrenetrisulphonate), and conventional oxygen equilibrium studies, data suggest that the binding of inositolhexaphosphate (IHP) to oxyHbC differs from HbA, indicating perturbations of the oxyHbC central cavity, which was predicted from our earlier spectroscopic findings. To define the relationship between this conformational change in oxyHbC and its tendency to crystallize, the effect of four central cavity ligands on the crystallization rate was studied: a peptide containing 11 residues from the N-terminal portion of band 3, the full cytoplasmic domain of band 3, 2,3-diphosphoglycerate and IHP. OxyHbC crystallization was accelerated by all these central cavity ligands and not by the appropriate controls. These central cavity changes become an excellent candidate for the dramatic increase in the crystallization rate of oxyHbC.

KW - Band 3

KW - Crystallization kinetics

KW - Diphosphoglyceric acid

KW - Fluorescence

KW - HbC

UR - http://www.scopus.com/inward/record.url?scp=0030929566&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030929566&partnerID=8YFLogxK

M3 - Article

VL - 98

SP - 583

EP - 588

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 3

ER -