HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 46, 38740-38755, November 18, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/46/38740    most recent M506333200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dantsker, D. Articles by Friedman, J. M. Search for Related Content PubMed PubMed Citation Articles by Dantsker, D. Articles by Friedman, J. M. Social Bookmarking                      What's this?

The Position 68(E11) Side Chain in Myoglobin Regulates Ligand Capture, Bond Formation with Heme Iron, and Internal Movement into the Xenon Cavities^*

David Dantsker, Camille Roche, Uri Samuni1, George Blouin, John S. Olson, and Joel M. Friedman2

From the Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461 and the Department of Biochemistry and Cell Biology and the W. M. Keck Center for Computational Biology, Rice University, Houston, Texas 77005-1892

After photodissociation, ligand rebinding to myoglobin exhibits complex kinetic patterns associated with multiple first-order geminate recombination processes occurring within the protein and a simpler bimolecular phase representing second-order ligand rebinding from the solvent. A smooth transition from cryogenic-like to solution phase properties can be obtained by using a combination of sol-gel encapsulation, addition of glycerol as a bathing medium, and temperature tuning (-15 65 °C). This approach was applied to a series of double mutants, myoglobin CO (H64L/V68X, where X = Ala, Val, Leu, Asn, and Phe), which were designed to examine the contributions of the position 68(E11) side chain to the appearance and disappearance of internal rebinding phases in the absence of steric and polar interactions with the distal histidine. Based on the effects of viscosity, temperature, and the stereochemistry of the E11 side chain, the three major phases, B A, C A, and D A, can be assigned, respectively, to ligand rebinding from the following: (i) the distal heme pocket, (ii) the xenon cavities prior to large amplitude side chain conformational relaxation, and (iii) the xenon cavities after significant conformational relaxation of the position 68(E11) side chain. The relative amplitudes of the B A and C A phases depend markedly on the size and shape of the E11 side chain, which regulates sterically both ligand return to the heme iron atom and ligand migration to the xenon cavities. The internal xenon cavities provide a transient docking site that allows side chain relaxations and the entry of water into the vacated distal pocket, which in turn slows ligand recombination markedly.

Received for publication, June 10, 2005 , and in revised form, August 29, 2005.

^* This work was supported in part by National Institutes of Health Program Project Grants PO1 GM58890 (to J. M. F.) and RO1 EB00296 (to J. M. F.), National Institutes of Health Grants GM35649 (to J. S. O.) and HL47020 (to J. S. O.), and Robert A. Welch Foundation Grant C-0612 (to J. S. O.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Recipient of Fellowship GM 08280 from the Houston Area Molecular Biophysics Pre-doctoral Training Program.

² To whom correspondence should be addressed: Dept. of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461. Tel.: 718-430-3591; Fax: 718-430-8819; E-mail: jfriedma{at}aecom.yu.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. H. Ouellet, R. Daigle, P. Lague, D. Dantsker, M. Milani, M. Bolognesi, J. M. Friedman, and M. Guertin Ligand Binding to Truncated Hemoglobin N from Mycobacterium tuberculosis Is Strongly Modulated by the Interplay between the Distal Heme Pocket Residues and Internal Water J. Biol. Chem., October 3, 2008; 283(40): 27270 - 27278. [Abstract] [Full Text] [PDF]

				J. Cohen and K. Schulten O2 Migration Pathways Are Not Conserved across Proteins of a Similar Fold Biophys. J., November 15, 2007; 93(10): 3591 - 3600. [Abstract] [Full Text] [PDF]

				C. J. Roche, D. Dantsker, U. Samuni, and J. M. Friedman Nitrite Reductase Activity of Sol-Gel-encapsulated Deoxyhemoglobin: INFLUENCE OF QUATERNARY AND TERTIARY STRUCTURE J. Biol. Chem., December 1, 2006; 281(48): 36874 - 36882. [Abstract] [Full Text] [PDF]

				J. Cohen, A. Arkhipov, R. Braun, and K. Schulten Imaging the Migration Pathways for O2, CO, NO, and Xe Inside Myoglobin Biophys. J., September 1, 2006; 91(5): 1844 - 1857. [Abstract] [Full Text] [PDF]

				R. A. Goldbeck, S. Bhaskaran, C. Ortega, J. L. Mendoza, J. S. Olson, J. Soman, D. S. Kliger, and R. M. Esquerra Water and ligand entry in myoglobin: Assessing the speed and extent of heme pocket hydration after CO photodissociation PNAS, January 31, 2006; 103(5): 1254 - 1259. [Abstract] [Full Text] [PDF]