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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Jurado AR,Huang CS,Zhang X,Zhou ZH,Tong L

doi

10.1038/ncomms9986

subject

Has Abstract

pub_date

2015-11-23 00:00:00

pages

8986

issn

2041-1723

pii

ncomms9986

journal_volume

6

pub_type

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