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Nat Commun. 2015 Nov 23;6:8986. doi: 10.1038/ncomms9986.

Structure and substrate selectivity of the 750-kDa α6β6 holoenzyme of geranyl-CoA carboxylase.

Author information

1
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
2
California NanoSystems Institute, University of California, Los Angeles, California 90095, USA.
3
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.

Abstract

Geranyl-CoA carboxylase (GCC) is essential for the growth of Pseudomonas organisms with geranic acid as the sole carbon source. GCC has the same domain organization and shares strong sequence conservation with the related biotin-dependent carboxylases 3-methylcrotonyl-CoA carboxylase (MCC) and propionyl-CoA carboxylase (PCC). Here we report the crystal structure of the 750-kDa α6β6 holoenzyme of GCC, which is similar to MCC but strikingly different from PCC. The structures provide evidence in support of two distinct lineages of biotin-dependent acyl-CoA carboxylases, one carboxylating the α carbon of a saturated organic acid and the other carboxylating the γ carbon of an α-β unsaturated acid. Structural differences in the active site region of GCC and MCC explain their distinct substrate preferences. Especially, a glycine residue in GCC is replaced by phenylalanine in MCC, which blocks access by the larger geranyl-CoA substrate. Mutation of this residue in the two enzymes can change their substrate preferences.

PMID:
26593090
PMCID:
PMC4673880
DOI:
10.1038/ncomms9986
[Indexed for MEDLINE]
Free PMC Article

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