*****************************************
* Putative AMP-binding domain signature *
*****************************************

It has been shown [1 to 5] that a number of prokaryotic and eukaryotic enzymes
which all probably act via  an ATP-dependent  covalent binding of AMP to their
substrate, share a region of sequence similarity. These enzymes are:

 - Insects luciferase (luciferin 4-monooxygenase)  (EC 1.13.12.7).  Luciferase
   produces light by catalyzing the oxidation of luciferin in  presence of ATP
   and molecular oxygen.
 - Alpha-aminoadipate  reductase (EC 1.2.1.31) from  yeast  (gene LYS2).  This
   enzyme catalyzes  the activation  of  alpha-aminoadipate  by  ATP-dependent
   adenylation and the reduction of activated alpha-aminoadipate by NADPH.
 - Acetate--CoA ligase (EC 6.2.1.1)  (acetyl-CoA synthetase),  an  enzyme that
   catalyzes the formation of acetyl-CoA from acetate and CoA.
 - Long-chain-fatty-acid--CoA  ligase  (EC 6.2.1.3), an  enzyme that activates
   long-chain fatty acids for both the synthesis of cellular lipids and  their
   degradation via beta-oxidation.
 - 4-coumarate--CoA ligase (EC 6.2.1.12) (4CL), a plant enzyme  that catalyzes
   the formation  of  4-coumarate-CoA from  4-coumarate  and  coenzyme A;  the
   branchpoint  reactions  between   general  phenylpropanoid  metabolism  and
   pathways leading to various specific end products.
 - O-succinylbenzoic acid--CoA ligase (EC 6.2.1.26) (OSB-CoA synthetase) (gene
   menE) [6], a bacterial enzyme  involved  in the biosynthesis of menaquinone
   (vitamin K2).
 - 4-Chlorobenzoate--CoA  ligase   (EC 6.2.1.-)  (4-CBA--CoA  ligase)  [7],  a
   Pseudomonas enzyme involved in the degradation of 4-CBA.
 - Indoleacetate--lysine ligase (EC 6.3.2.20) (IAA-lysine synthetase) [8],  an
   enzyme from Pseudomonas syringae that converts indoleacetate to IAA-lysine.
 - Bile acid-CoA  ligase  (gene baiB)  from  Eubacterium strain VPI 12708 [4].
   This enzyme catalyzes the ATP-dependent formation of a variety of C-24 bile
   acid-CoA.
 - L-(alpha-aminoadipyl)-L-cysteinyl-D-valine  synthetase   (ACV   synthetase)
   from Penicillium chrysogenum (gene acvA).  This  enzyme catalyzes the first
   step in the biosynthesis of penicillin and cephalosporin,  the formation of
   ACV from the constituent amino acids.  The amino acids seem to be activated
   by adenylation. acvA is a  protein of  3746 amino acids that contains three
   related domains of about 600 amino acids.
 - Gramicidin S synthetase I (gene grsA)  from  Bacillus brevis.  This  enzyme
   catalyzes the first step  in  the  biosynthesis  of  the  cyclic antibiotic
   gramicidin S, the ATP-dependent racemization of phenylalanine (EC 5.1.1.11)
 - Tyrocidine synthetase I (gene tycA)  from  Bacillus  brevis.   The reaction
   carried out by tycA is identical to that catalyzed by grsA
 - Gramicidin S synthetase II (gene grsB)  from  Bacillus brevis. This  enzyme
   is a  multifunctional  protein  that  activates  and  polymerizes  proline,
   valine, ornithine and leucine.  GrsB consists  of  four  related domains of
   about 600 amino acids.
 - Enterobactin synthetase  components E (gene entE)  and  F (gene entF)  from
   Escherichia coli.  These  two  enzymes  are  involved  in the ATP-dependent
   activation  of  respectively   2,3-dihydroxybenzoate   and   serine  during
   enterobactin (enterochelin) biosynthesis.

There are also some proteins, whose exact function is not yet known, but which
are, very probably, also AMP-binding enzymes. These proteins are:

 - ORA  (octapeptide-repeat antigen),  a Plasmodium falciparum  protein  whose
   function is not known but which  shows a high degree of similarity with the
   above proteins.
 - AngR, a Vibrio anguillarum protein. AngR is thought to be a transcriptional
   activator  which  modulates  the  anguibactin (an iron-binding siderophore)
   biosynthesis gene  cluster operon.  But  we believe [9], that angR is not a
   DNA-binding protein, but rather an  enzyme involved in  the biosynthesis of
   anguibactin.  This conclusion is  based on three facts: the presence of the
   AMP-binding domain; the size of angR (1048 residues),  which is far  bigger
   than any bacterial transcriptional protein; and  the presence of a probable
   S-acyl thioesterase immediately downstream of angR.
 - A hypothetical protein in mmsB 3'region in Pseudomonas aeruginosa.
 - Escherichia coli hypothetical protein yaaM.

All these proteins contains a highly  conserved  region  very rich in glycine,
serine, and threonine  which is  followed  by a conserved lysine.   A parallel
can be drawn [9]  between  this type of  domain and  the G-x(4)-G-K-[ST] ATP-/
GTP-binding 'P-loop' domain or  the protein kinases G-x-G-x(2)-[SG]-x(10,20)-K
ATP-binding domains (see the relevant sections).

-Consensus pattern: [LIVMFY]-x(2)-[STG](2)-G-[ST]-[STE]-[SG]-x-[PALIVM]-K
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in SWISS-PROT: 5.

-Note: in a majority of cases the residue that  follows  the Lys at the end of
 the pattern is a Gly.

-Last update: October 1993 / Pattern and text revised.

[ 1] Toh H.
     Protein Seq. Data Anal. 4:111-117(1991).
[ 2] Smith D.J., Earl A.J., Turner G.
     EMBO J. 9:2743-2750(1990).
[ 3] Schroeder J.
     Nucleic Acids Res. 17:460-460(1989).
[ 4] Mallonee D.H., Adams J.L., Hylemon P.B.
     J. Bacteriol. 174:2065-2071(1992).
[ 5] Turgay K., Krause M., Marahiel M.A.
     Mol. Microbiol. 6:529-546(1992).
[ 6] Driscoll J.R., Taber H.W.
     J. Bacteriol. 174:5063-5071(1992).
[ 7] Babbitt P.C., Kenyon G.L., Matin B.M., Charest H., Sylvestre M.,
     Scholten J.D., Chang K.-H., Liang P.-H., Dunaway-Mariano D.
     Biochemistry 31:5594-5604(1992).
[ 8] Farrell D.H., Mikesell P., Actis L.A., Crosa J.H.
     Gene 86:45-51(1990).
[ 9] Bairoch A.
     Unpublished observations (1991).