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Crystal Structure of the Acidaminococcus fermentans 2-hydroxyglutaryl-CoA Dehydratase Component A

Locher, Kaspar P. and Hans, Marcus and Yeh, Andrew P. and Schmid, Benedikt and Buckel, Wolfgang and Rees, Douglas C. (2001) Crystal Structure of the Acidaminococcus fermentans 2-hydroxyglutaryl-CoA Dehydratase Component A. Journal of Molecular Biology, 307 (1). pp. 297-308. ISSN 0022-2836. doi:10.1006/jmbi.2000.4496.

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Acidaminococcus fermentans degrades glutamate via the hydroxyglutarate pathway, which involves the syn-elimination of water from (R)-2-hydroxyglutaryl-CoA in a key reaction of the pathway. This anaerobic process is catalyzed by 2-hydroxyglutaryl-CoA dehydratase, an enzyme with two components (A and D) that reversibly associate during reaction cycles. Component A (CompA), a homodimeric protein of 2x27 kDa, contains a single, bridging [4Fe-4S] cluster and uses the hydrolysis of ATP to deliver an electron to the dehydratase component (CompD), where the electron is used catalytically. The structure of the extremely oxygen-sensitive CompA protein was solved by X-ray crystallography to 3 Å resolution. The protein was found to be a member of the actin fold family, revealing a similar architecture and nucleotide-binding site. The key differences between CompA and other members of the actin fold family are: (i) the presence of a cluster binding segment, the “cluster helix”; (ii) the [4Fe-4S] cluster; and (iii) the location of the homodimer interface, which involves the bridging cluster. Possible reaction mechanisms are discussed in light of the close structural similarity to members of the actin-fold family and the functional similarity to the nitrogenase Fe-protein.

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Rees, Douglas C.0000-0003-4073-1185
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Additional Information:© 2001 Academic Press. Received 12 December 2000; received in revised form 25 January 2001; accepted 25 January 2001. We thank J. B. Howard for stimulating discussions and National Institutes of Health grant GM45162 to D.C.R. and Deutsche Forschungsgemeinschaft grants to W. B. and to M.H. for support of this research.
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Deutsche Forschungsgemeinschaft (DFG)UNSPECIFIED
Subject Keywords:actin fold; hexokinase; heat shock protein 70; ATP hydrolysis; electron transfer
Issue or Number:1
Record Number:CaltechAUTHORS:20150108-153550607
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Official Citation:Kaspar P Locher, Marcus Hans, Andrew P Yeh, Benedikt Schmid, Wolfgang Buckel, Douglas C Rees, Crystal structure of the Acidaminococcus fermentans 2-hydroxyglutaryl-CoA dehydratase component A, Journal of Molecular Biology, Volume 307, Issue 1, 16 March 2001, Pages 297-308, ISSN 0022-2836, (
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ID Code:53406
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Deposited On:08 Feb 2015 06:40
Last Modified:10 Nov 2021 20:01

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