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Abstract
The Molybdenum cofactor (Moco) biosynthesis pathway is an evolutionary conserved pathway seen in almost all eukaryotes including the pathogenic species Mycobacterium tuberculosis. This pathway comprises of several novel reactions which include the initial formation of precursor Z from guanosine triphosphate (GTP), catalysed by two enzymes MoaA and MoaC. Although Moco biosynthesis is well understood, the first step is still not clear. In M. tuberculosis H37Rv, three orthologous genes of MoaC have been annotated: moaC1 (Rv3111), moaC2 (Rv0864) and moaC3 (Rv3324c). Rv0864 (MoaC2) is a 17.5 kDa protein and is reported to be down-regulated by ∼3 times in the nutrient starvation model for Mycobacterium tuberculosis. The crystal structure of Moco-biosynthesis protein MoaC2 from Mycobacterium tuberculosis (2.20 Å resolution, space group P213) has been determined. Based on a comparative analysis of structures of homologous proteins, conserved residues were identified and are implicated in structural and functional roles. Molecular docking studies with probable ligands carried out in order to identify its ligand, suggests that pteridinebenzomonophosphate as the most likely ligand. Sequence based interaction study identified MoaA1 to interact with MoaC2. A homology model of MoaA1 was then complexed with MoaC2 and protein–protein interactions are also discussed.
Highlights
Rv0864 (MoaC2) from Mycobacterium tuberculosis is one of the enzymes in the molybdenum cofactor (Moco) biosynthesis pathway
Together with MoaA, MoaC is involved in the conversion of guanosine triphosphate (GTP) to precursor Z, the first step in Moco synthesis [1,2]
The Structure of moaC3 (Rv3324c). Rv0864 (MoaC2) The MoaC2 monomer has a common a+b protein fold that is composed of a four stranded anti-parallel b-sheet and three helices, a1, a 2 and a3 located underneath the b-sheet (Figure 2 a)
Summary
Rv0864 (MoaC2) from Mycobacterium tuberculosis is one of the enzymes in the molybdenum cofactor (Moco) biosynthesis pathway. Kanaujia et al, (2010) [8] proposed that the formation of precursor Z can occur in two possible pathways: in the first path where FPT (formamidopyrimidine-type) is the substrate of MoaC [7] and precursor Z is formed either via the formation of intermediate compound E (formamido-type) or PBM (pteridinebenzomonophosphate), and in the second case, compound PBT (pteridinebenzotriphosphate) may play the role of the substrate of MoaC which is formed when the ring formation of FPT molecule is completed. In this pathway, PBM is the intermediate formed before precursor Z (Figure 1)
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