Table 1.
Conserved sequence motifs
| Corea | Motifb | Consensus Sequencec | Position d |
Role |
|---|---|---|---|---|
| A1 | θ(S/T)ϕx(E/Q)θ | Leu30 | Structural Role. Caps a helix at N- terminus of the protein. |
|
| A2 | (R/K/F)θGθ | Arg76 | Structural Role. Torsion angles enforce a glycine at position 78 |
|
| A3 | I | θθx(S/T)(S/T/G)G(S/T)TGxP K |
Ile158 | Phosphate-binding loop, orienting the β,γ- phosphates. |
| A4 | ϕ | His207 | Active site aromatic residue that alternates conformation in the two enzyme states and caps a helix that forms part of the acyl-binding pocket |
|
| A5 | II | ϕ(G/W)x(A/T)E | Tyr304 | Initial aromatic residue stacks agains adenine ring of ATP, Gly or Trp forms wall of active site, Glu binds the Mg2+ ion. |
| A6 | GEx10-14GY | Gly351 | Structural Role. Forms a portion of the distorted β-sheet of the N-terminal domain |
|
| A7 | III | (S/T)GD | Ser383 | The Asp of this motif binds the ribose hydroxyls of ATP and is 100% conserved |
| A8 | Rx(D/K)x6G | Arg400 | The Arg interacts with ribose hydroxyls. The Asp (or rarely Lys) is the hinge residue. The Gly abuts the pantetheine tunnel in the thioester-forming conformation. |
|
| A9 | No conservation within larger family |
|||
| A10 | Px4GKθx(R/K) | Pro486 | The first lysine (Lys492) is present at the active site in the adenylate-forming conformation. |
a
Core sequence as defined by Marahiel et al (38) for NRPS adenylation domains
b
Motif defined by Chang et al (37) for aromatic adenylate forming ligases
c
Single amino acid code, θ is used for medium aliphatic amino acids (A,V,L,I,M). ϕ is used for aromatic amino acids (F,Y,H,W).
d
Position is provided for the first amino acid residue of the motif in the representative enzyme 4-Chlorobenzoyl-CoA Ligase.