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

J. Biol. Chem., Vol. 281, Issue 17, 11471-11479, April 28, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/17/11471    most recent M512054200v1 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 Das, T. K. Articles by Rousseau, D. L. Search for Related Content PubMed PubMed Citation Articles by Das, T. K. Articles by Rousseau, D. L. Social Bookmarking                      What's this?

Multiple Active Site Conformers in the Carbon Monoxide Complexes of Trematode Hemoglobins^*

Tapan K. Das, Sylvia Dewilde¹, Joel M. Friedman^¶, Luc Moens, and Denis L. Rousseau^¶2

From the Pfizer Global Biologics, Chesterfield, Missouri 63017, the Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium, and the ^¶Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461

Sequence alignment of hemoglobins of the trematodes Paramphistomum epiclitum and Gastrothylax crumenifer with myoglobin suggests the presence of an unusual active site structure in which two tyrosine residues occupy the E7 and B10 helical positions. In the crystal structure of P. epiclitum hemoglobin, such an E7-B10 tyrosine pair at the putative helical positions has been observed, although the E7 Tyr is displaced toward CD region of the polypeptide. Resonance Raman data on both P. epiclitum and G. crumenifer hemoglobins show that interactions of heme-bound ligands with neighboring amino acid residues are unusual. Multiple conformers in the CO complex, termed the C, O, and N conformers, are observed. The conformers are separated by a large difference (60 cm^–1) in the frequencies of their Fe-CO stretching modes. In the C conformer the Fe-CO stretching frequency is very high, 539 and 535 cm^–1, for the P. epiclitum and G. crumenifer hemoglobins, respectively. The Fe-CO stretching of the N conformer appears at an unusually low frequency, 479 and 476 cm^–1, respectively, for the two globins. A population of an O conformer is seen in both hemoglobins, at 496 and 492 cm^–1, respectively. The C conformer is stabilized by a strong polar interaction of the CO with the distal B10 tyrosine residue. The O conformer is similar to the ones typically seen in mutant myoglobins in which there are no strong interactions between the CO and residues in the distal pocket. The N conformer possesses an unusual configuration in which a negatively charged group, assigned as the oxygen atom of the B10 Tyr side chain, interacts with the CO. In this conformer, the B10 Tyr assumes an alternative conformation consistent with one of the conformers seen the crystal structure. Implications of the multiple configurations on the ligand kinetics are discussed.

Received for publication, November 8, 2005 , and in revised form, February 14, 2006.

^* This work was supported by National Institutes of Health Grants GM54806 (to D. L. R.) and GM58890 (to J. M. F.). 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.

¹ Postdoctoral fellow of the Fund for Scientific Research Flanders (FWO).

² To whom correspondence should be addressed: Dept. of Physiology and Biophysics, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Ave., Bronx, NY 10461. Tel.: 718-430-4264; Fax: 718-430-8808; E-mail: rousseau{at}aecom.yu.edu.

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

This article has been cited by other articles:

				C. Lu, M. Mukai, Y. Lin, G. Wu, R. K. Poole, and S.-R. Yeh Structural and Functional Properties of a Single Domain Hemoglobin from the Food-borne Pathogen Campylobactor jejuni J. Biol. Chem., August 31, 2007; 282(35): 25917 - 25928. [Abstract] [Full Text] [PDF]