title: 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.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Peterson
authors.forename: Roman
authors.initials: R
authors.lastname: Shinder
authors.forename: Imran
authors.initials: I
authors.lastname: Khan
authors.forename: Laura
authors.initials: L
authors.lastname: Juczszak
authors.forename: Jiaqian
authors.initials: J
authors.lastname: Wang
authors.forename: Belur
authors.initials: B
authors.lastname: Manjula
authors.forename: Seetharama A
authors.initials: SA
authors.lastname: Acharya
authors.forename: Celia
authors.initials: C
authors.lastname: Bonaventura
authors.forename: Joel M
authors.initials: JM
authors.lastname: Friedman
mesh_terms: 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
chemical_list: 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