Bonding of molecular oxygen to T state human haemoglobin

Brzozowski, A.M.; Derewenda, Zygmunt S.; Dodson, E.J.; Dodson, Guy; Grabowski, M. J.; Liddington, Robert; Skarżyński, T.; Vallely, David

doi:10.1038/307074a0

Cited by 102 publications

(51 citation statements)

References 13 publications

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“…¶ This notation identifies the fully liganded R2 state of human Hb. spite the extensive use of a variety of experimental techniques (19,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). In this context, the mixed structure of HbTn[␣(CO)␤(hemi)] 2 herewith reported displays a number of interesting features.…”

Section: Discussionmentioning

confidence: 89%

The crystal structure of a tetrameric hemoglobin in a partial hemichrome state

Riccio

Vitagliano

Prisco

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Tetrameric hemoglobins are the most widely used systems in studying protein cooperativity. Allosteric effects in hemoglobins arise from the switch between a relaxed (R) state and a tense (T) state occurring upon oxygen release. Here we report the 2.0-Å crystal structure of the main hemoglobin component of the Antarctic fish Trematomus newnesi, in a partial hemichrome form. The two ␣-subunit iron atoms are bound to a CO molecule, whereas in the ␤ subunits the distal histidine residue is the sixth ligand of the heme iron. This structure, a tetrameric hemoglobin in the hemichrome state, demonstrates that the iron coordination by the distal histidine, usually associated with denaturing states, may be tolerated in a native-like hemoglobin structure. In addition, several features of the tertiary and quaternary organization of this structure are intermediate between the R and T states and agree well with the R 3 T transition state properties obtained by spectroscopic and kinetic techniques. The analysis of this structure provides a detailed pathway of heme-heme communication and it indicates that the plasticity of the ␤ heme pocket plays a role in the R 3 T transition of tetrameric hemoglobins.protein denaturation ͉ protein function ͉ x-ray structure ͉ Antarctic

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Section: Discussionmentioning

confidence: 89%

The crystal structure of a tetrameric hemoglobin in a partial hemichrome state

Riccio

Vitagliano

Prisco

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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“…In the past 10 years, it has become possible to crystallize Hb under conditions where the crystals do not shatter upon changing the degree of ligation. In this method, deoxygenated Hb A was crystallized from solutions of polyethylene glycol (28,29) and the X-ray crystal structures showed that the molecules remained in the T state and that the salt bridges remained intact over the full range of oxygen tension from 9 to 700 Torr. The crystallographic results surprisingly showed that only the ® chains were ligated even at the high oxygen pressure.…”

Section: Do the Salt Bridges Break Upon Ligation?mentioning

confidence: 99%

Spectroscopic Contributions to the Understanding of Hemoglobin Function: Implications for Structural Biology

Shulman¹

2001

IUBMB Life

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“…We will also compare the energetics with crystallographic results (3,4 (6)(7)(8). The thermodynamic coupling between ligand binding and reversible dissociation of tetramers into dimers has thus proved to be a powerful means of measuring cooperative free energies (5)(6)(7)(8).…”

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confidence: 99%

Three-state combinatorial switching in hemoglobin tetramers: comparison between functional energetics and molecular structures.

Smith

Gingrich

Hoffman

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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In a previous study on cyanomethemoglobin the 10 tetrameric species (each with a unique combination of ligated and unligated subunits) were found to exhibit three distinct free energies of cooperative interaction. The distribution of these free energies among the partially ligated species is incompatible with a two-state mechanism of molecular switching and requires a minimum of three molecular structures with distinctly different free energies of heme-heme interaction. Ligand-linked transitions between the three cooperativity states were found to be "combinatorial"-i.e., dependent upon changes in both the number and specific configuration of bound ligands. Here we present results from two other chemical systems that mimic intermediate oxygenation states. In these systems the heme iron is replaced by manganese in certain of the subunits. We find the same distribution of cooperative free energies as reported for the cyanomethemoglobin system. These results demonstrate that the three-state combinatorial nature of cooperative switching is neither a special feature of the cyanomet reactions nor of the substitution of manganese for iron, but reflects a fundamental property of hemoglobin. These findings are compared with crystallographic structural results on partially ligated hemoglobins. (Fig. 2). In view of the potential significance of these findings to the mechanism of hemoglobin cooperativity, it is essential to determine whether three-state combinatorial switching is a special property of the cyanomet reactions with hemoglobin and whether the three levels of cooperativity correspond to distinct molecular structures. In the present study we determined the cooperative free energies for partially ligated tetramers in two additional, chemically different, systems that mimic partially ligated tetramers. The species we have studied are depicted in Fig. 3: in system A the hemes are replaced in some of the subunits by Mn2+ protoporphyrin IX, providing a functional analog of unligated subunits (2, 14) while the remaining subunits have normal hemes that are ligated with carbon monoxide (CO); in system B, the unligated subunits contain normal heme while the ligated subunits contain hemes replaced by Mn3+ protoporphyrin IX. 01Here we analyze the functional energetics of these systems in terms of the minimum number of molecular structures required. We will also compare the energetics with crystallographic results (3, 4). AG, = AGi -iAG~,where AGQ is the standard Gibbs free energy for reacting i moles of ligand with a tetramer and AG. is the intrinsic free energy per site for the same reaction in the absence of cooperativity (5). In hemoglobin tetramers iAGx generally has a larger negative value (higher affinity) than AG, so that AGc is positive. A finding that AGc = 3.0 kcal (1 cal = 4.18 J) for Abbreviation: MWC, Monod-Wyman-Changeux. 7089The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §173...

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Bonding of molecular oxygen to T state human haemoglobin

Cited by 102 publications

References 13 publications

The crystal structure of a tetrameric hemoglobin in a partial hemichrome state

The crystal structure of a tetrameric hemoglobin in a partial hemichrome state

Spectroscopic Contributions to the Understanding of Hemoglobin Function: Implications for Structural Biology

Three-state combinatorial switching in hemoglobin tetramers: comparison between functional energetics and molecular structures.

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