Protein Family Models

Family members were previously thought to be ArgK proteins acting as ATPase enzymes and kinases. They are now believed to be methylmalonyl Co-A mutase-associated GTPase MeaB. Structural studies of MeaB and the human ortholog (methylmalonyl associated protein A) MMAA, reveal alpha-helical domains at the N- and C-termini as well as a Ras-like GTPase domain. Mutational analysis of MeaB, show prohibited growth in Methylobacterium due to the inability to convert methylmalonyl-CoA to succinyl-CoA caused by an inactive form of methylmalonyl-CoA mutatase (mcm). In humans, mutations in (MMAA) are associated with the fatal disease methylmalonyl aciduria [1]. [1]. 25832174. Crystal structures of Mycobacterial MeaB and MMAA-like GTPases. Edwards TE, Baugh L, Bullen J, Baydo RO, Witte P, Thompkins K, Phan IQ, Abendroth J, Clifton MC, Sankaran B, Van Voorhis WC, Myler PJ, Staker BL, Grundner C, Lorimer DD;. J Struct Funct Genomics. 2015;16:91-99. (from Pfam)

Date:

2024-10-16

This domain is found in HypB, a hydrogenase expression / formation protein, and UreG a urease accessory protein. Both these proteins contain a P-loop nucleotide binding motif [2,3]. HypB has GTPase activity and is a guanine nucleotide binding protein [3]. It is not known whether UreG binds GTP or some other nucleotide. Both enzymes are involved in nickel binding. HypB can store nickel and is required for nickel dependent hydrogenase expression [1]. UreG is required for functional incorporation of the urease nickel metallocenter.[4] GTP hydrolysis may required by these proteins for nickel incorporation into other nickel proteins [1]. This family of domains also contains P47K (Swiss:P31521), a Pseudomonas chlororaphis protein needed for nitrile hydratase expression, and the cobW gene product (Swiss:P29937), which may be involved in cobalamin biosynthesis in Pseudomonas denitrificans [5]. [1]. 9140970. The HypB protein from Bradyrhizobium japonicum can store nickel and is required for the nickel-dependent transcriptional regulation of hydrogenase. Olson JW, Fu C, Maier RJ;. Mol Microbiol 1997;24:119-128. [2]. 9209019. Characterization of UreG, identification of a UreD-UreF-UreG complex, and evidence suggesting that a nucleotide-binding site in UreG is required for in vivo metallocenter assembly of Klebsiella aerogenes urease. Moncrief MB, Hausinger RP;. J Bacteriol 1997;179:4081-4086. [3]. 8423137. The product of the hypB gene, which is required for nickel incorporation into hydrogenases, is a novel guanine nucleotide-binding protein. Maier T, Jacobi A, Sauter M, Bock A;. J Bacteriol 1993;175:630-635. [4]. 1624427. Klebsi. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-10-16

ArgK/MeaB family GTPase such as human mitochondrial methylmalonic aciduria type A protein, mycobacterial methylmalonyl Co-A mutase-associated GTPase MeaB, and Escherichia coli GTPase ArgK

Date:

2018-03-02

In E. coli, mutation of this kinase blocks phosphorylation of two transporter system periplasmic binding proteins and consequently inhibits those transporters. This kinase is also found in Gram-positive bacteria, archaea, and the roundworm C. elegans. It may have a more general, but still unknown function. Mutations have also been found that do not phosphorylate the periplasmic binding proteins, yet still allow transport. The ATPase activity of this protein seems to be necessary, however.

Gene:

meaB

Date:

2024-05-30

Gene:

meaB

Date:

2021-07-30