Target intelligence / Profile preview

Adenosylcobinamide-GDP ribazoletransferase (CobS)

Target
CobS
Molecular classification
Enzyme, Transferase, Phosphotransferase
01

Overview

Adenosylcobinamide-GDP ribazoletransferase, commonly known as Cobalamin synthase or CobS, is a critical enzyme in the biosynthetic pathway of Vitamin B12 (cobalamin) in bacteria and archaea [4, 5]. It catalyzes the final step of the pathway: the condensation of adenosylcobinamide-GDP with alpha-ribazole to form adenosylcobalamin [2, 6]. This enzyme is essential for microorganisms that rely on de novo B12 synthesis for vital processes such as DNA synthesis and amino acid metabolism [13, 17]. Because humans lack the entire cobalamin biosynthetic machinery and must obtain the vitamin from their diet, CobS represents a promising target for the development of novel, selective antibacterial agents [14, 20]. Inhibition of this enzyme would disrupt B12 production in pathogens like Mycobacterium tuberculosis, potentially leading to bacterial growth inhibition without affecting human host cells [13, 14]. While no clinical drugs currently target CobS, it remains a focal point in research aimed at overcoming antimicrobial resistance by targeting unique bacterial metabolic pathways [19, 21].

Other names
Cobalamin synthaseCobalamin-5'-phosphate synthaseAdenosylcobalamin synthaseAdenosylcobinamide-alpha-ribazole adenosyltransferaseCobSCobV
02

Mechanism of action

Inhibition of cobalamin biosynthesis

03

Biological functions

Cobalamin biosynthesisVitamin B12 metabolismNucleotide loop assembly
04

Disease associations

InfectionTuberculosis
05

Safety considerations

Minimal human toxicity due to the absence of the cobalamin biosynthetic pathway in humansPotential theoretical interference with host B12 utilization or transport mechanisms
06

Biomarkers

Intracellular cobalamin (Vitamin B12) levelsBacterial growth inhibitionExpression levels of cobS mRNA

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