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Crystallographic studies of the Escherichia coli quinol-fumarate reductase with inhibitors bound to the quinol-binding site

Iverson, Tina M. and Luna-Chavez, César and Croal, Laura R. and Cecchini, Gary and Rees, Douglas C. (2002) Crystallographic studies of the Escherichia coli quinol-fumarate reductase with inhibitors bound to the quinol-binding site. Journal of Biological Chemistry, 277 (18). pp. 16124-16130. ISSN 0021-9258. https://resolver.caltech.edu/CaltechAUTHORS:IVEjbc02

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Abstract

The quinol-fumarate reductase (QFR) respiratory complex of Escherichia coli is a four-subunit integral-membrane complex that catalyzes the final step of anaerobic respiration when fumarate is the terminal electron acceptor. The membrane-soluble redox-active molecule menaquinol (MQH(2)) transfers electrons to QFR by binding directly to the membrane-spanning region. The crystal structure of QFR contains two quinone species, presumably MQH(2), bound to the transmembrane-spanning region. The binding sites for the two quinone molecules are termed Q(P) and Q(D), indicating their positions proximal Q(P)) or distal (Q(D)) to the site of fumarate reduction in the hydrophilic flavoprotein and iron-sulfur protein subunits. It has not been established whether both of these sites are mechanistically significant. Co-crystallization studies of the E. coli QFR with the known quinol-binding site inhibitors 2-heptyl-4-hydroxyquinoline-N-oxide and 2-[1-(p-chlorophenyl)ethyl] 4,6-dinitrophenol establish that both inhibitors block the binding of MQH(2) at the Q(P) site. In the structures with the inhibitor bound at Q(P), no density is observed at Q(D), which suggests that the occupancy of this site can vary and argues against a structurally obligatory role for quinol binding to Q(D). A comparison of the Q(P) site of the E. coli enzyme with quinone-binding sites in other respiratory enzymes shows that an acidic residue is structurally conserved. This acidic residue, Glu-C29, in the E. coli enzyme may act as a proton shuttle from the quinol during enzyme turnover.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1074/jbc.M200815200DOIUNSPECIFIED
ORCID:
AuthorORCID
Rees, Douglas C.0000-0003-4073-1185
Additional Information:Copyright © 2002 by the American Society for Biochemistry and Molecular Biology. Received for publication, January 25, 2002, and in revised form, February 15, 2002. We thank A. P. Yeh, R. B. Bass, and A. Dunn for experimental assistance, H. Miyoshi for generously providing the DNP-19 inhibitor compound, Y. F. C. Lau for providing sequences of the mouse SQR before publication, C. L. Drennan and D. Ringe for the use of computer facilities, and T. Ohnishi, I. Schroder, P. L. Dutton, H. B. Gray, and R. A. Marcus for enlightening discussions.
Subject Keywords:CYTOCHROME BC(1) COMPLEX; SUCCINATE-UBIQUINONE OXIDOREDUCTASE; ANCHORING SUBUNIT QPS3; WOLINELLA-SUCCINOGENES; PROTON-TRANSFER; RESPIRATORY COMPLEX; ELECTRON-TRANSPORT; HEART-MITOCHONDRIA; CATALYTIC ACTIVITY; DEHYDROGENASE
Issue or Number:18
Record Number:CaltechAUTHORS:IVEjbc02
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:IVEjbc02
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:4846
Collection:CaltechAUTHORS
Deposited By: Lindsay Cleary
Deposited On:11 Sep 2006
Last Modified:02 Oct 2019 23:16

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