{PDOC51191}
{PS51191; FEMABX}
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* FemABX peptidyl transferase family profile *
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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 [1-4].

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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: March 2006 / First entry.

[ 1] Hegde S.S., Shrader T.E.
     "FemABX family members are novel nonribosomal peptidyltransferases and
     important pathogen-specific drug targets."
     J. Biol. Chem. 276:6998-7003(2001).
     PubMed=11083873; DOI=10.1074/jbc.M008591200
[ 2] Rohrer S., Berger-Bachi B.
     "FemABX peptidyl transferases: a link between branched-chain cell wall
     peptide formation and beta-lactam resistance in gram-positive cocci."
     Antimicrob. Agents Chemother. 47:837-846(2003).
     PubMed=12604510
[ 3] Hegde S.S., Blanchard J.S.
     "Kinetic and mechanistic characterization of recombinant Lactobacillus
     viridescens FemX (UDP-N-acetylmuramoyl pentapeptide-lysine
     N6-alanyltransferase)."
     J. Biol. Chem. 278:22861-22867(2003).
     PubMed=12679335; DOI=10.1074/jbc.M301565200
[ 4] Biarrotte-Sorin S., Maillard A.P., Delettre J., Sougakoff W.,
     Arthur M., Mayer C.
     "Crystal structures of Weissella viridescens FemX and its complex with
     UDP-MurNAc-pentapeptide: insights into FemABX family substrates
     recognition."
     Structure 12:257-267(2004).
     PubMed=14962386; DOI=10.1016/j.str.2004.01.006

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