It has been shown [1,2,3,4,5] 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 126.96.36.199). Luciferase
produces light by catalyzing the oxidation of luciferin in presence of ATP
and molecular oxygen.
α-aminoadipate reductase (EC 188.8.131.52) from yeast (gene LYS2). This
enzyme catalyzes the activation of α-aminoadipate by ATP-dependent
adenylation and the reduction of activated α-aminoadipate by NADPH.
Acetate--CoA ligase (EC 184.108.40.206) (acetyl-CoA synthetase), an enzyme that
catalyzes the formation of acetyl-CoA from acetate and CoA.
Long-chain-fatty-acid--CoA ligase (EC 220.127.116.11), an enzyme that activates
long-chain fatty acids for both the synthesis of cellular lipids and their
degradation via β-oxidation.
4-coumarate--CoA ligase (EC 18.104.22.168) (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 22.214.171.124) (OSB-CoA synthetase) (gene
menE) , a bacterial enzyme involved in the biosynthesis of menaquinone
4-Chlorobenzoate--CoA ligase (EC 6.2.1.-) (4-CBA--CoA ligase) , a
Pseudomonas enzyme involved in the degradation of 4-CBA.
Indoleacetate--lysine ligase (EC 126.96.36.199) (IAA-lysine synthetase) , an
enzyme from Pseudomonas syringae that converts indoleacetate to IAA-lysine.
Bile acid-CoA ligase (gene baiB) from Eubacterium strain VPI 12708 .
This enzyme catalyzes the ATP-dependent formation of a variety of C-24 bile
Crotonoβine/carnitine-CoA ligase (EC 6.3.2.-) from Escherichia coli
L-(α-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACV synthetase)
from various fungi (gene acvA or pcbAB). 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. It is a protein of around 3700 amino acids that contains
three related domains of about 1000 amino acids.
Gramicidin S synthase 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 188.8.131.52)
Tyrocidine synthase I (gene tycA) from Bacillus brevis. The reaction
carried out by tycA is identical to that catalyzed by grsA
Gramicidin S synthase 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.
Enterobactin synthase 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.
Cyclic peptide antibiotic surfactin synthase subunits 1, 2 and 3 from
Bacillus subtilis. Subunits 1 and 2 contains three related domains while
subunit 3 only contains a single domain.
HC-toxin synthetase (gene HTS1) from Cochliobolus carbonum. This enzyme
activates the four amino acids (Pro, L-Ala, D-Ala and 2-amino-9,10-epoxi-8-
oxodecanoic acid) that make up HC-toxin, a cyclic tetrapeptide. HTS1
consists of four related domains.
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
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 , 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 ydiD.
Yeast hypothetical protein YBR041w.
Yeast hypothetical protein YBR222c.
Yeast hypothetical protein YER147c.
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  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 <PDOC00017> and <PDOC00100>).
In a majority of cases the residue that follows the Lys at the end of
the pattern is a Gly.
December 2004 / Pattern and text revised.
PROSITE method (with tools and information) covered by this documentation:
Sequence analysis of firefly luciferase family reveals a conservative sequence motif.
The multifunctional peptide synthetase performing the first step of penicillin biosynthesis in Penicillium chrysogenum is a 421,073 dalton protein similar to Bacillus brevis peptide antibiotic synthetases.
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