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The Functional, Oxygen-linked Chloride Binding Sites Of Hemoglobin Are Contiguous Within A Channel In The Central Cavity

H. Ueno, J. Manning
Published 1992 · Chemistry, Medicine

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Chloride ion is a major allosteric regulator for many hemoglobins and particularly for bovine hemoglobin. A site-directed reagent for amino groups, methyl acetyl phosphate, when used forglobal rather thanselective modification of R (oxy) and T (deoxy) state bovine hemoglobin, can acetylate those functional amino groups involved in binding of chloride; the extensively acetylated hemoglobin tetramer retains nearly full cooperativity. The chloride-induced decrease in the oxygen affinity parallels the acetylation of bovine hemoglobin (i.e., their effects are mutually exclusive), suggesting that methyl acetyl phosphate is a good probe for the functional chloride binding sites in hemoglobins. Studies on theoverall alkaline Bohr effect indicates that the part of the contribution dependent on chloride and reduced by 60% after acetylation is due to amino groups, Val-1(α) and Lys-81(β); the remaining 40% is contributed by the imidazole side chain of His-146(β), which is not acetylated by methyl acetyl phosphate, and is not dependent on chloride. The five amino groups—Val-1(α), Lys-99(α), Met-1(β), Lys-81(β), and Lys-103(β)—of bovine hemoglobin that are acetylated in an oxygen-linked fashion are consideredfunctional chloride binding sites. Molecular modeling indicates that these functional chloride binding sites are contiguous from one end of the central cavity of hemoglobin to the other; some of them are aligned within a chloride channel connecting each end of the dyad axis. A generalization that can be made about hemoglobin function from these studies is that the blocking of positive charges within this channel either by binding of chloride or other anions, by covalent chemical modification such as acetylation, or by site-specific mutagenesis to create additional chloride binding sites each accomplish the same function of lowering the oxygen affinity of hemoglobin.
This paper references
The pK of Specific Groups of Proteins I. THE α-AMINO GROUP OF THE α CHAIN OF HUMAN CO-HEMOGLOBIN
R. E. Hill (1967)
10.1021/BI00560A010
Changes in pKa values of individual histidine residues of human hemoglobin upon reaction with carbon monoxide.
M. Ohe (1980)
10.1038/237146A0
X-ray Diffraction Study of Binding of 2,3-Diphosphoglycerate to Human Deoxyhaemoglobin
A. Arnone (1972)
10.1073/PNAS.88.8.3329
Preparation, properties, and plasma retention of human hemoglobin derivatives: comparison of uncrosslinked carboxymethylated hemoglobin with crosslinked tetrameric hemoglobin.
L. Manning (1991)
10.1016/0022-2836(80)90312-5
Regulation of oxygen affinity of mammalian haemoglobins.
M. Perutz (1980)
10.1016/S0022-2836(65)80285-6
ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL.
J. Monod (1965)
10.1016/s0021-9258(17)40546-1
Quantitative determination of carbamino adducts of alpha and beta chains in human adult hemoglobin in presence and absence of carbon monoxide and 2,3-diphosphoglycerate.
J. Matthew (1977)
10.1021/BI00394A001
How much do we know about the Bohr effect of hemoglobin?
C. Ho (1987)
10.1021/JO00296A056
Dicarboxylic acid bis(methyl phosphates): anionic biomimetic crosslinking reagents
R. Kluger (1990)
10.1021/BI00266A027
Mechanism for the increase in solubility of deoxyhemoglobin S due to cross-linking the beta chains between lysine-82 beta 1 and lysine-82 beta 2.
R. Chatterjee (1982)
10.1016/s0021-9258(19)70585-7
Structural and functional studies of hemoglobin Suresnes (arg 141 alpha 2 replaced by His beta 2). Consequences of disrupting an oxygen-linked anion-binding site.
C. Poyart (1980)
10.1038/NBT0191-57
Synthesis of Wild Type and Mutant Human Hemoglobins in Saccharomyces cerevisiae
M. Wagenbach (1991)
10.1016/s0021-9258(18)67605-7
Isolation and characterization of a new hemoglobin derivative cross-linked between the alpha chains (lysine 99 alpha 1----lysine 99 alpha 2).
R. Chatterjee (1986)
10.1126/science.172.3987.1049
Differences in the Interaction of 2,3-Diphosphoglycerate with Certain Mammalian Hemoglobins
H. Bunn (1971)
10.1016/s0021-9258(19)41315-x
Determination of the pK values for the alpha-amino groups of human hemoglobin.
M. Garner (1975)
10.3109/03630268209083759
Detection of Hb-Papio B, a silent mutation of the baboon beta chain, by high performance liquid chromatography. Improved procedures for the separation of globin chains by HPLC.
J. B. Shelton (1982)
10.1016/0003-9861(86)90648-X
Site-specific modification of hemoglobin by methyl acetyl phosphate.
H. Ueno (1986)
10.1021/BI00458A024
New effectors of human hemoglobin: structure and function.
I. Lalezari (1990)
10.1016/S0022-2836(75)80037-4
Three-dimensional fourier synthesis of human deoxyhaemoglobin at 2-5 A resolution: refinement of the atomic model.
G. Fermi (1975)
10.1016/s0021-9258(17)32899-5
Reactivity of cyanate with valine-1 (alpha) of hemoglobin. A probe of conformational change and anion binding.
A. M. Nigen (1976)
10.1017/s0033583500003826
Mechanisms of Cooperativity and Allosteric Regulation in Proteins
M. Perutz (1990)
10.1021/BI00323A020
Anion Bohr effect of human hemoglobin.
E. Bucci (1985)
10.1021/JM00106A042
Allosteric modifiers of hemoglobin. 2. Crystallographically determined binding sites and hydrophobic binding/interaction analysis of novel hemoglobin oxygen effectors.
F. Wireko (1991)
10.1016/0022-2836(72)90566-9
Nuclear magnetic resonance quadrupole relaxation studies of chloride binding to human oxy- and deoxyhaemoglobin.
E. Chiancone (1972)
10.1021/jo01301a039
Methyl acetyl phosphate. A small anionic acetylating agent
R. Kluger (1980)
10.1016/s0021-9258(17)43552-6
Involvement of His HC3 (146) beta in the Bohr effect of human hemoglobin. Studies of native and N-ethylmaleimide-treated hemoglobin A and hemoglobin Cowtown (beta 146 His replaced by Leu).
T. Shih (1984)
10.1016/0022-2836(88)90463-9
Modulation of oxygen affinity in hemoglobin by solvent components. Interaction of bovine hemoglobin with 2,3-diphosphoglycerate and monatomic anions.
C. Fronticelli (1988)
10.1016/S0022-2836(80)80022-2
Identification of residues contributing to the Bohr effect of human haemoglobin.
M. Perutz (1980)
10.1038/228726A0
Stereochemistry of Cooperative Effects in Haemoglobin: Haem–Haem Interaction and the Problem of Allostery
M. Perutz (1970)



This paper is referenced by
10.1016/S0301-4622(96)02236-3
Tertiary and quaternary chloride effects of the partially ligated (CN-met) hemoglobin intermediates.
Y. Huang (1997)
10.1080/02648725.1992.10647894
Blood substitutes: engineering the haemoglobin molecule.
K. Vandegriff (1992)
10.1074/jbc.273.31.19359
Normal and Abnormal Protein Subunit Interactions in Hemoglobins*
J. Manning (1998)
10.1007/978-1-4612-2576-8_6
Design of Chemically Modified and Recombinant Hemoglobins as Potential Red Cell Substitutes
J. Manning (1995)
10.1016/J.JMB.2005.12.018
R-state haemoglobin with low oxygen affinity: crystal structures of deoxy human and carbonmonoxy horse haemoglobin bound to the effector molecule L35.
Takeshi Yokoyama (2006)
10.1002/9780470166482.CH6
Metal Ion Reconstituted Hybrid Hemoglobins
B. Venkatesh (2007)
10.1016/J.RVSC.2004.02.004
Haemoglobin oxygen affinity and regulating factors of the blood oxygen transport in canine and feline blood.
C. Cambier (2004)
10.1016/J.JMB.2009.01.038
Using multiconformation continuum electrostatics to compare chloride binding motifs in alpha-amylase, human serum albumin, and Omp32.
Y. Song (2009)
10.1016/S0968-0004(99)01395-X
Remote contributions to subunit interactions: lessons from adult and fetal hemoglobins.
J. Manning (1999)
10.1016/j.cbpa.2014.06.012
Enthalpic partitioning of the reduced temperature sensitivity of O2 binding in bovine hemoglobin.
R. E. Weber (2014)
10.1016/0076-6879(94)31016-5
Preparation of hemoglobin derivatives selectively or randomly modified at amino groups.
J. Manning (1994)
10.1529/BIOPHYSJ.104.046136
Liganded hemoglobin structural perturbations by the allosteric effector L35.
Q. Chen (2005)
10.1002/PRO.5560040104
A recombinant human hemoglobin with asparagine‐102(β) substituted by alanine has a limiting low oxygen affinity, reduced marginally by chloride
H. Yanase (1995)
10.1016/S0006-3495(01)75845-6
Molecular dynamics analysis of a second phosphate site in the hemoglobins of the seabird, south polar skua. Is there a site-site migratory mechanism along the central cavity?
A. Riccio (2001)
10.1093/CARCIN/17.12.2661
Structural characterization by mass spectrometry of hemoglobin adducts formed after in vivo exposure to methyl bromide.
P. Ferranti (1996)
10.1016/S1246-7820(96)80026-7
Examples of chemical modification and recombinant DNA approaches with hemoglobin.
J. Manning (1996)
10.1002/PRO.5560030807
Properties of a recombinant human hemoglobin with aspartic acid 99 (β), an important intersubunit contact site, substituted by lysine
Hideshi Yanase (1994)
10.3109/10731199409117414
Random chemical modification of hemoglobin to identify chloride binding sites in the central dyad axis: their role in control of oxygen affinity.
J. Manning (1994)
10.1002/pro.3359
Contributions to nucleosome dynamics in chromatin from interactive propagation of phosphorylation/acetylation and inducible histone lysine basicities
L. Manning (2018)
10.1006/BCMD.2002.0546
Distinct domain responses of R-state human hemoglobins A, C, and S to anions.
Q. Chen (2002)
10.1074/jbc.M303352200
Human Erythrocyte Membrane Band 3 Protein Influences Hemoglobin Cooperativity
Y. Zhang (2003)
contact site, substituted by lysine
H. Yanase (1994)
10.1007/BF01025120
Random chemical modification of the oxygen-linked chloride-binding sites of hemoglobin: Those in the central dyad axis may influence the transition between deoxy- and oxy-hemoglobin
H. Ueno (1993)
10.1016/S0301-4622(96)02235-1
Effects of NaCl on the linkages between O2 binding and subunit assembly in human hemoglobin: titration of the quaternary enhancement effect.
M. Doyle (1997)
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