PROSITE documentation PDOC51191

FemABX peptidyl transferase family profile

FemABX peptidyl transferases (EC 2.3.2.-) catalyze the incorporation of amino acid(s) into the interchain peptide bridge of peptidoglycan using aminoacyl-tRNA as the amino acid donor, a reaction involved in the synthesis of the bacterial cell wall. The femABX transferases are named after Staphylococcus aureus femA and femB (from factors essential for methicillin resistance) and Weissella viridescens femX. The femABX enzymes catalyze the addition of amino acids to a peptidoglycan precursor, which in most cases is a lipid-linked sugar pentapeptide or, alternatively, a soluble nucleotide precursor for W. viridescens femX. The resulting branched peptide chain consists of one to five amino acids and is cross-linked to a pentapeptide of a neighboring disaccharide chain by a transpeptidase in the final step of peptidoglycan synthesis. The interchain peptide and the femABX enzymes for their synthesis are found in several Gram-positive bacteria and in some Gram-negative, mainly pathogenic species. The femABX transferases differ by type, position and number of amino acids that are incoporated into the interchain. Some femABX proteins function as immunity factors that protect producers of interpeptide-specific endopeptidases against their own products. In addition, the interpeptide plays an important role in cell separation and virulence [1,2,3,4].

The 3D structures of femABX peptidyl transferases consist of two subdomains which both show a fold related to that of Gcn5-related N-acetyltransferases (GNAT) (see <PDOC51186>). The C-terminus of the protein structurally partakes in the N-terminal subdomain, and the C-terminal subdomain shows stronger similarity to the GNAT fold. In femX the 2 subdomains are separated by a cleft containing the UDP-MurNac pentapeptide binding site; the N-terminal subdomain contributes to this binding site and the C-terminal subdomain may be involved in tRNA binding (see <PDB:1NE9>) [4]. An antiparallel coiled-coil region of 60 residues occurs within the C-terminal subdomain of femA (see <PDB:1LRZ>), which is replaced by a tight loop in femX. The coiled-coil region might be implicated in tRNA binding and is present in most of the femABX proteins from staphylococci, enterococci and streptococci.

Some proteins known to belong to the femABX peptidyl transferase family:

• Staphylococcal femA and femB, factors essential for expression of methicillin resistance. FemA adds glycines 2 and 3 of the pentaglycine interpeptide, while femB adds glycines 4 and 5.
• Staphylococcal fmhB (for fem homolog) or femX, which incorporates the first glycine of the pentaglycine interchain peptide in peptidoglycan.
• Weissella viridescens femX, which catalyzes the transfer of an L-alanine from Ala-tRNA to the epsilon-amino group of L-lysine of UDP-MurNAc pentapeptide [3,4].
• Streptococcus pneumoniae fibA/murM and fibB/murN, which synthesize branched structured cell wall muropeptides that are strain-specific.
• Staphylococcus capitis epr (endopeptidase resistance), which renders the cells resistant to glycylglycine endopeptidase by increasing the serine content and decreasing the glycine content of the interpeptide chains.

The profile we developed covers the entire femABX peptidyl transferase domain.