Sulfide-binding hemoglobins: effects of mutations on active-site flexibility

The dynamics of Hb I (HbI) from the clam Lucina pectinata, from wild-type sperm whale (SW) myoglobin, and from the L29F/H64Q/V68F triple mutant of SW, both unligated and bound to hydrogen sulfide (H2S), have been studied in mol. dynamics simulations. Features that account for differences in H2S affinity among the three have been examd. Our results verify the existence of an unusual heme rocking motion in unligated HbI that can promote the entrance of large ligands such as H2S. The FQF-mutant partially reproduces the amplitude and relative orientation of the motion of HbI's heme group. Therefore, besides introducing favorable electrostatic interactions with H2S, the three mutations in the distal pocket change the dynamic properties of the heme group. The active-site residues Gln-64(E7), Phe-43(CD1), and His-93(F8) are also shown to be more flexible in unligated HbI than in FQF-mutant and SW. Further contributions to H2S affinity come from differences in hydrogen bonding between the heme propionate groups and nearby amino acid residues. [on SciFinder (R)]


Published in:
Biophysical Journal, 91, 5, 1698-1709
Year:
2006
Keywords:
Note:
CAN 145:412687 6-3 General Biochemistry Universidad Nacional de Quilmes,Bernal,Argent. Journal 0006-3495 written in English. 7782-44-7 (Dioxygen) Role: BSU (Biological study, unclassified), BIOL (Biological study) (Hb binding; sulfide-binding Hbs and effects of mutations on active-site flexibility); 7783-06-4 (Hydrogen sulfide); 18496-25-8 (Sulfide) Role: BSU (Biological study, unclassified), BIOL (Biological study) (sulfide-binding Hbs and effects of mutations on active-site flexibility); 9034-85-9 (Hemoglobin I) Role: BSU (Biological study, unclassified), PRP (Properties), BIOL (Biological study) (sulfide-binding Hbs and effects of mutations on active-site flexibility)
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 Record created 2007-05-31, last modified 2018-03-18

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