Human Deoxyhaemoglobin-2,3-Diphosphoglycerate Complex Low-Salt Structure at 2·5 Å Resolution

R‐state hemoglobin bound to heterotropic effectors: models of the DPG, IHP and RSR13 binding sites

“…After minimization, the lowest-energy complexes were selected as best fit and submitted to molecular dynamics (MD) simulations for optimization of the HbA tertiary structure with docked effector. The docking results were controlled by also docking DPG to T-state HbA, which yielded best scores in all features similar to the published X-ray coordinates [30]: DPG also docked at the entrance of the cavity between the two b subunits as is the case in the X-ray structure site and the DPG solvent accessible surface area calculated for the best docked scores averaged 160.86 Å 2 (cf. 162.73 Å 2 for the X-ray structure).…”

“…The two classes of effectors modeled in this study, i.e., the anionic type (DPG, IHP) and the BZF-analog type (RSR13), do not bind the same type of site and it is noteworthy that this is also the case for the sites identified in the T-state-effector complexes for which X-ray structures are available [29][30][31]. Our modeling results are consistent with binding site specificity for both T-and R-state HbA in the central cavity: both T-state and R-state central cavities bind one anionic-type effector (DPG, IHP) and as for the clofibrate and BZF-analogs, T-state binds at least two effectors in the central cavity at primary and secondary sites, while R-state binds one in its central cavity.…”

“…Initial coordinates were obtained from the RCSB repository, namely 1HHO (R-state HbA) [27], 2HHB (T-state HbA) [28], 1THB (T-state-IHP complex) [29], 1B86 (T-state-DPG complex) [30], and 1G9V (Tstate-RSR13 complex) [31]. The 1HHO structure contains only one dimer and the second was constructed by symmetry to obtain tetrameric R-HbA.…”

“…The first site identified was that of the natural effector present in red blood cells, 2,3-diphosphoglycerate (DPG), found to bind HbA in a 1:1 stoichiometry [4,5]. It is located at the entrance of the cavity between the two b-subunits that contribute positively charged residues to complement the negatively charged DPG phosphate groups, namely val1, his2 and lys82 of both b chains (Fig.…”

The Functionally Distinct Hemoglobins of the Arctic Spotted Wolffish Anarhichas minor

“…pH 8.0 was chosen because at this value Hb 3, unlike Hb 2, showed maximal difference in oxygen affinity in the presence of IHP. After minimization of the models, the ATP and IHP molecules were added by automated docking to the classical phosphate binding site of both Hbs in the central cavity located between the two ␤ chains of the deoxy form (21,22).…”