Domain-specific effector interactions within the central cavity of human adult hemoglobin in solution and in porous sol-gel matrices: evidence for long-range communication pathways.
The water-filled central cavity of human adult hemoglobin (Hb A) is the binding or interaction site for many different allosteric effectors. Oxygen binding titrations reveal that pyrenetetrasulfonate (PyTS), a fluorescent analogue of 2,3-diphosphoglycerate, behaves like an allosteric effector. The ligation state, pH, and concentrations of other effectors (IHP, L35, and chloride) alter PyTS fluorescence for both solution-phase and sol-gel-encapsulated Hb samples. These conditions also alter the resonance Raman spectra and rates of geminate recombination of CO-ligated Hb. Together, these results demonstrate that there are conformational and functional consequences resulting from interactions between specific domains of the central cavity and individual effectors as well as from long-range synergistic effects that are mediated through the central cavity.
Peterson
Eric S
ES
Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Shinder
Roman
R
Khan
Imran
I
Juczszak
Laura
L
Wang
Jiaqian
J
Manjula
Belur
B
Acharya
Seetharama A
SA
Bonaventura
Celia
C
Friedman
Joel M
JM
D000328:Adult; D000494:Allosteric Regulation; D000495:Allosteric Site; D002248:Carbon Monoxide / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D005782:Gels; D006441:Hemoglobin A / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D010100:Oxygen / Q000378:metabolism; D010671:Phenylurea Compounds / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011721:Pyrenes / Q000737:chemistry; D012996:Solutions; D013050:Spectrometry, Fluorescence; D013059:Spectrum Analysis, Raman
D005456:Fluorescent Dyes; D005782:Gels; D008024:Ligands; D010671:Phenylurea Compounds; D011721:Pyrenes; D012996:Solutions; C064070:L 35; D002248:Carbon Monoxide; D006441:Hemoglobin A; C041343:1,3,6,8-pyrene tetrasulfonate; D010100:Oxygen