Target intelligence / Profile preview

Acetyl-CoA carboxylase subunit alpha (accA3) (ACCA3)

Target
ACCA3
Molecular classification
Enzyme, Ligase, Carboxylase
01

Overview

MAP_3404 is a gene in Mycobacterium avium subsp. paratuberculosis (MAP) that encodes the biotin carboxylase (BC) subunit, also known as accA3, of the acetyl-CoA carboxylase (ACC) enzyme complex [2], [10]. This enzyme system is responsible for the first committed and rate-limiting step in fatty acid biosynthesis, where it catalyzes the ATP-dependent carboxylation of acetyl-CoA to produce malonyl-CoA [10], [12]. In mycobacteria, malonyl-CoA is a vital precursor for the synthesis of long-chain fatty acids and mycolic acids, which are critical structural components of the unique, lipid-rich cell wall that facilitates bacterial survival and virulence within host macrophages [3], [8]. MAP is the causative agent of Johne's disease, a chronic and debilitating inflammatory bowel disease in ruminants, and has been extensively studied for its potential role in human Crohn's disease [1], [3]. Because the bacterial ACC complex is essential for cell wall integrity and possesses structural differences from eukaryotic counterparts, MAP_3404 is considered a highly promising target for the development of novel antimycobacterial drugs [6], [7]. Furthermore, the protein product of MAP_3404 is highly antigenic and has been identified as a key target for monoclonal antibodies used in diagnostic ELISAs to detect MAP infection in livestock [2], [4].

Other names
MAP_3404Biotin carboxylase subunit of acetyl-CoA carboxylaseaccA3Acetyl-CoA carboxylase subunit A 3BC subunit
02

Mechanism of action

Inhibition of the biotin carboxylase activity of the acetyl-CoA carboxylase complex, preventing the conversion of acetyl-CoA to malonyl-CoA and subsequently halting the biosynthesis of essential mycolic acids.

03

Biological functions

Fatty acid biosynthesisCell wall synthesisBiotin metabolic processCarbon fixation
04

Disease associations

InfectionJohne's diseaseCrohn's disease
05

Safety considerations

Selectivity over host acetyl-CoA carboxylase isoforms (ACACA and ACACB)Potential for off-target metabolic disruption in the host
06

Interacting drugs

Acetyl-CoA carboxylase inhibitors (experimental)
07

Biomarkers

MAP_3404-specific antibodiesAnti-MAP IgG

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