Crystal structure of the Acidaminococcus fermentans 2-hydroxyglutaryl-CoA dehydratase component A.
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 A 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.
Howard Hughes Medical Institute, Division of Chemistry and Chemical Engineering, California Institute of Technology, Mail Code 147-75CH, Pasadena, CA 91125, USA.
K P
KP
Locher
M
M
Hans
A P
AP
Yeh
B
B
Schmid
W
W
Buckel
D C
DC
Rees
D000199:Actins / Q000737:chemistry; D000244:Adenosine Diphosphate / Q000737:chemistry; D000595:Amino Acid Sequence; D001407:Bacillus / Q000737:chemistry* / Q000201:enzymology; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D006836:Hydro-Lyases / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009591:Nitrogenase / Q000737:chemistry; D009711:Nucleotides / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid
D000199:Actins; D009711:Nucleotides; D000244:Adenosine Diphosphate; D009591:Nitrogenase; C054464:2-hydroxyglutaryl-CoA dehydratase; D006836:Hydro-Lyases