Crystal structure of the Acidaminococcus fermentans 2-hydroxyglutaryl-CoA dehydratase component A

Acidaminococcus fermentans degrades glutamate via the hydroxyglutarate path way, 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] clus ter and uses the hydrolysis of ATP to deliver an electron to the dehydratas e component (CompD), where the electron is used catalytically. The structur e of the extremely oxygen-sensitive CompA protein was solved by X-ray cryst allography to 3 Angstrom resolution. The protein was found to be a member o f the actin fold family, revealing a similar architecture and nucleotide-bi nding site. The key differences between CompA and other members of the acti n fold family are: (i) the presence of a cluster binding segment, the "clus ter helix"; (ii) the [4Fe-4S] cluster; and (iii) the location of the homodi mer interface, which involves the bridging cluster. Possible reaction mecha nisms are discussed in light of the close structural similarity to members of the actin-fold family and the functional similarity to the nitrogenase F e-protein. (C) 2001 Academic Press.