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 binds to B12 (adenosylcobamide)[1-3], it is found in several enzymes, such as glutamate mutase Swiss:Q05488, methionine synthase Swiss:Q99707 and methylmalonyl-CoA mutase Swiss:P22033. It contains a conserved DxHxxGx(41)SxVx(26)GG motif, which is important for B12 binding [2]. [1]. 9739092. How a protein prepares for B12 binding: structure and dynamics of the B12-binding subunit of glutamate mutase from Clostridium tetanomorphum. Tollinger M, Konrat R, Hilbert BH, Marsh EN, Krautler B;. Structure 1998;6:1021-1033. [2]. 11914353. Role for vitamin B(12) in light induction of gene expression in the bacterium Myxococcus xanthus. Cervantes M, Murillo FJ;. J Bacteriol. 2002;184:2215-2224. [3]. 18315685. Vitamin B12 partners the CarH repressor to downregulate a photoinducible promoter in Myxococcus xanthus. Perez-Marin MC, Padmanabhan S, Polanco MC, Murillo FJ, Elias-Arnanz M;. Mol Microbiol. 2008;67:804-819. (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

The enzyme methylmalonyl-CoA mutase is a member of a class of enzymes that uses coenzyme B12 (adenosylcobalamin) as a cofactor. The enzyme induces the formation of an adenosyl radical from the cofactor. This radical then initiates a free-radical rearrangement of its substrate, succinyl-CoA, to methylmalonyl-CoA [1]. [1]. 8805541. How coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 A resolution. Mancia F, Keep NH, Nakagawa A, Leadlay PF, McSweeney S, Rasmussen B, Bosecke P, Diat O, Evans PR;. Structure 1996;4:339-350. (from Pfam)

Date:

2024-10-16

Gene:

icmF

Date:

2023-11-09

Methylmalonyl-CoA mutase (EC 5.4.99.2) catalyzes a reversible isomerization between L-methylmalonyl-CoA and succinyl-CoA. The enzyme uses an adenosylcobalamin cofactor. It may be a homodimer, as in mitochondrion, or a heterodimer with partially homologous beta chain that does not bind the adenosylcobalamin cofactor, as in Propionibacterium freudenreichii. The most similar archaeal sequences are separate chains, such as AF2215 abd AF2219 of Archaeoglobus fulgidus, that correspond roughly to the first 500 and last 130 residues, respectively of known methylmalonyl-CoA mutases. This HMM describes the N-terminal domain subfamily. In a neighbor-joining tree, AF2215 branches with a bacterial isobutyryl-CoA mutase, which is also the same length. Scoring between the noise and trusted cutoffs are the non-catalytic, partially homologous beta chains from certain heterodimeric examples of 5.4.99.2.

Date:

2024-05-30