| Structural highlights
Function
CAR_NOCIO Catalyzes the reduction of a very wide range of aliphatic carboxylic acids as well as many aryl carboxylic acids into their corresponding aldehydes, by using ATP for energy to drive the reaction. Aryl carboxylic acid substrates include substituted benzoic acids, phenyl-substituted aliphatic acids, heterocyclic carboxylic acids, and polyaromatic ring carboxylic acids. Cannot reduce benzaldehyde to benzyl alcohol.[1] [2] [3] [4]
Publication Abstract from PubMed
Carboxylic acid reductase (CAR) catalyzes the ATP- and NADPH-dependent reduction of carboxylic acids to the corresponding aldehydes. The enzyme is related to the nonribosomal peptide synthetases, consisting of an adenylation domain fused via a peptidyl carrier protein (PCP) to a reductase termination domain. Crystal structures of the CAR adenylation-PCP didomain demonstrate that large-scale domain motions occur between the adenylation and thiolation states. Crystal structures of the PCP-reductase didomain reveal that phosphopantetheine binding alters the orientation of a key Asp, resulting in a productive orientation of the bound nicotinamide. This ensures that further reduction of the aldehyde product does not occur. Combining crystallography with small-angle X-ray scattering (SAXS), we propose that molecular interactions between initiation and termination domains are limited to competing PCP docking sites. This theory is supported by the fact that (R)-pantetheine can support CAR activity for mixtures of the isolated domains. Our model suggests directions for further development of CAR as a biocatalyst.
Structures of carboxylic acid reductase reveal domain dynamics underlying catalysis.,Gahloth D, Dunstan MS, Quaglia D, Klumbys E, Lockhart-Cairns MP, Hill AM, Derrington SR, Scrutton NS, Turner NJ, Leys D Nat Chem Biol. 2017 Sep;13(9):975-981. doi: 10.1038/nchembio.2434. Epub 2017 Jul , 17. PMID:28719588[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ He A, Li T, Daniels L, Fotheringham I, Rosazza JP. Nocardia sp. carboxylic acid reductase: cloning, expression, and characterization of a new aldehyde oxidoreductase family. Appl Environ Microbiol. 2004 Mar;70(3):1874-81. PMID:15006821
- ↑ Venkitasubramanian P, Daniels L, Rosazza JP. Reduction of carboxylic acids by Nocardia aldehyde oxidoreductase requires a phosphopantetheinylated enzyme. J Biol Chem. 2007 Jan 5;282(1):478-85. Epub 2006 Nov 13. PMID:17102130 doi:http://dx.doi.org/10.1074/jbc.M607980200
- ↑ Li T, Rosazza JP. Purification, characterization, and properties of an aryl aldehyde oxidoreductase from Nocardia sp. strain NRRL 5646. J Bacteriol. 1997 Jun;179(11):3482-7. PMID:9171390
- ↑ Li T, Rosazza JP. Purification, characterization, and properties of an aryl aldehyde oxidoreductase from Nocardia sp. strain NRRL 5646. J Bacteriol. 1997 Jun;179(11):3482-7. PMID:9171390
- ↑ Gahloth D, Dunstan MS, Quaglia D, Klumbys E, Lockhart-Cairns MP, Hill AM, Derrington SR, Scrutton NS, Turner NJ, Leys D. Structures of carboxylic acid reductase reveal domain dynamics underlying catalysis. Nat Chem Biol. 2017 Sep;13(9):975-981. doi: 10.1038/nchembio.2434. Epub 2017 Jul , 17. PMID:28719588 doi:http://dx.doi.org/10.1038/nchembio.2434
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