Modeling of ligation-induced helix/loop displacements in myoglobin: toward an understanding of hemoglobin allostery

Journal of the American Chemical Society
Victor GuallarThomas G Spiro

Abstract

Combining quantum and molecular mechanics (QM/MM) methods and protein structure prediction algorithms, helix and loop movements are computed along the pathway of CO dissociation from myoglobin (Mb). The results are compared with high-resolution crystallographic data using sequence-displacement graphs. These graphs provide an unbiased method for evaluating main-chain segmental motions; they resolve an apparent disagreement between two sets of high-resolution crystal structures for MbCO and deoxyMb. The QM/MM modeling of the CO deligation reproduces the experimentally observed spin states and photodissociated crystal structure. The principal effect of CO dissociation is shown to be a concerted rotation of the E and F helices, which hold the heme like a clamshell. The rotation is a response to deligation forces, which impel the F helix away from the heme because of the Fe spin conversion, and which allow the E helix to collapse toward the heme as nonbonded contacts on the distal side are relieved. Additional helix and loop displacements stem from these primary events. In particular, the CD loop is found to be repositioned as a result of steric interactions with the water molecule that becomes H-bonded to the distal histidine in de...Continue Reading

References

Apr 5, 1979·Journal of Molecular Biology·J Baldwin, C Chothia
May 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·A Warshel
Apr 23, 1991·Biochemistry·P J SteinbachD C Lamb
May 15, 1984·Journal of Molecular Biology·G FermiR Fourme
Jul 1, 1998·Annual Review of Biophysics and Biomolecular Structure·M F PerutzG G Dodson
Apr 16, 1999·Science·G S KachalovaH D Bartunik
Oct 8, 1999·Biophysical Journal·J VojtechovskýI Schlichting
Mar 27, 2001·Accounts of Chemical Research·T G Spiro, P M Kozlowski
Jul 5, 2002·Journal of Molecular Biology·Matthew P JacobsonBarry Honig
Jul 18, 2002·Journal of Inorganic Biochemistry·Emma Sigfridsson, Ulf Ryde
Jan 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jonathan A LukinChien Ho
Mar 6, 2004·Journal of Molecular Biology·Victor GuallarRichard A Friesner
Mar 30, 2004·Proteins·Matthew P JacobsonRichard A Friesner
Jul 9, 2004·Journal of the American Chemical Society·Victor Guallar, Richard A Friesner
Oct 9, 2004·Faraday Discussions·Jeremy N Harvey
Jan 6, 2005·Journal of the American Chemical Society·Karin NienhausG Ulrich Nienhaus
Mar 8, 2005·Biophysical Journal·Sandra MaguidJulian Echave
Mar 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Victor Guallar, Kenneth W Borrelli
Jul 21, 2006·The Journal of Physical Chemistry. B·Filippo De AngelisThomas G Spiro

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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 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·R E AlcantaraV Guallar
May 23, 2007·Proceedings of the National Academy of Sciences of the United States of America·Akira SatoYasuhisa Mizutani
Jul 3, 2010·Journal of Molecular Biology·M CammarataA Cupane
Apr 20, 2010·Biophysical Chemistry·Victor Guallar, Frank H Wallrapp
May 1, 2007·Biophysical Journal·Massimiliano AnselmiAlfredo Di Nola
Jul 9, 2008·Current Opinion in Structural Biology·Gurusamy BalakrishnanThomas G Spiro
Mar 6, 2012·Biophysical Journal·M Fátima Lucas, Víctor Guallar
Jan 29, 2009·Angewandte Chemie·Hans Martin Senn, Walter Thiel
Nov 21, 2008·The Journal of Biological Chemistry·Victor GuallarSyun-Ru Yeh
Mar 23, 2011·Journal of Computational Chemistry·Yang Liu, Huai Sun
Jun 9, 2020·The Journal of Physical Chemistry. B·Shinya TaharaYasuhisa Mizutani
Jun 8, 2010·The Journal of Physical Chemistry. B·Damián E BikielDarío A Estrin
Apr 19, 2019·Journal of Chemical Information and Modeling·Wanlei WeiNicolas Moitessier

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