Hemoglobin site-mutants reveal dynamical role of interhelical H-bonds in the allosteric pathway: time-resolved UV resonance Raman evidence for intra-dimer coupling

Journal of Molecular Biology
Gurusamy BalakrishnanThomas G Spiro

Abstract

The dynamical effect of eliminating specific tertiary H-bonds in the hemoglobin (Hb) tetramer has been investigated by site-directed mutagenesis and time-resolved absorption and ultraviolet resonance Raman (UVRR) spectroscopy. The Trp alpha 14...Thr alpha 67 and Trp beta 15...Ser beta 72 H-bonds connect the A and E helices in the alpha and beta chains, and are proposed to break in the earliest protein intermediate (Rdeoxy) following photo-deligation of HbCO, along with a second pair of H-bonds involving tyrosine residues. Mutation of the acceptor residues Thr alpha 67 and Ser beta 72 to Val and Ala eliminates the A-E H-bonds, but has been shown to have no significant effect on ligand-binding affinity or cooperativity, or on spectroscopic markers of the T-state quaternary interactions. However, the mutations have profound and unexpected effects on the character of the Rdeoxy intermediate, and on the dynamics of the subsequent steps leading to the T state. Formation of the initial quaternary contact (RT intermediate) is accelerated, by an order of magnitude, but the locking-in of the T state is delayed by a factor of 2. These rate effects are essentially the same for either mutation, or for the double mutation, suggesting that th...Continue Reading

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Citations

Mar 17, 2009·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Gurusamy BalakrishnanThomas G Spiro
Nov 15, 2007·Inorganic Chemistry·Thomas G Spiro
Dec 18, 2010·The Journal of Physical Chemistry. B·Eva MeirovitchJack H Freed
Nov 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·R E AlcantaraV Guallar
Jan 7, 2016·Chemical Reviews·George P Lisi, J Patrick Loria
Jul 3, 2010·Journal of Molecular Biology·M CammarataA Cupane
Dec 22, 2005·Journal of Molecular Biology·Janina KneippThomas G Spiro
Jul 9, 2008·Current Opinion in Structural Biology·Gurusamy BalakrishnanThomas G Spiro
Aug 2, 2005·Applied Spectroscopy·Gurusamy BalakrishnanThomas G Spiro
Aug 15, 2015·Physical Chemistry Chemical Physics : PCCP·Cheolhee YangHyotcherl Ihee
Dec 21, 2017·Physical Chemistry Chemical Physics : PCCP·Shanyan ChangYasuhisa Mizutani
Apr 3, 2013·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Noriko InoguchiHideaki Moriyama
Jan 21, 2006·The Journal of Biological Chemistry·Gary K Ackers, Jo M Holt
Jan 14, 2012·Journal of the American Chemical Society·Yuka MurakawaYasuhisa Mizutani
Jan 22, 2015·Chemical Reviews·Yue YuanChien Ho
Aug 2, 2013·The Journal of Physical Chemistry. B·Heng-I KanChia C Wang

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